IKIP downregulates THBS1/FAK signaling to suppress migration and invasion by glioblastoma cells.

Background: Inhibitor of NF-κB kinase-interacting protein (IKIP) is known to promote proliferation of glioblastoma (GBM) cells, but how it affects migration and invasion by those cells is unclear. Methods: We compared levels of IKIP between glioma tissues and normal brain tissue in clinical samples and public databases. We examined the effects of IKIP overexpression and knockdown on the migration and invasion of GBM using transwell and wound healing assays, and we compared the transcriptomes under these different conditions to identify the molecular mechanisms involved. Results: Based on data from our clinical samples and from public databases, IKIP was overexpressed in GBM tumors, and its expression level correlated inversely with survival. IKIP overexpression in GBM cells inhibited migration and invasion in transwell and wound healing assays, whereas IKIP knockdown exerted the opposite effects. IKIP overexpression in GBM cells that were injected into mouse brain promoted tumor growth but inhibited tumor invasion of surrounding tissue. The effects of IKIP were associated with downregulation of THBS1 mRNA and concomitant inhibition of THBS1/FAK signaling. Conclusions: IKIP inhibits THBS1/FAK signaling to suppress migration and invasion of GBM cells.

Exosomal miR-17-5p derived from epithelial cells is involved in aberrant epithelium-fibroblast crosstalk and induces the development of oral submucosal fibrosis.

Oral submucous fibrosis (OSF) is a chronic and inflammatory mucosal disease caused by betel quid chewing, which belongs to oral potentially malignant disorders. Abnormal fibroblast differentiation leading to disordered collagen metabolism is the core process underlying OSF development. The epithelium, which is the first line of defense against the external environment, can convert external signals into pathological signals and participate in the remodeling of the fibrotic microenvironment. However, the specific mechanisms by which the epithelium drives fibroblast differentiation remain unclear. In this study, we found that Arecoline-exposed epithelium communicated with the fibrotic microenvironment by secreting exosomes. MiR-17-5p was encapsulated in epithelial cell-derived exosomes and absorbed by fibroblasts, where it promoted cell secretion, contraction, migration and fibrogenic marker (α-SMA and collagen type I) expression. The underlying molecular mechanism involved miR-17-5p targeting Smad7 and suppressing the degradation of TGF-ß receptor 1 (TGFBR1) through the E3 ubiquitination ligase WWP1, thus facilitating downstream TGF-ß pathway signaling. Treatment of fibroblasts with an inhibitor of miR-17-5p reversed the contraction and migration phenotypes induced by epithelial-derived exosomes. Exosomal miR-17-5p was confirmed to function as a key regulator of the phenotypic transformation of fibroblasts. In conclusion, we demonstrated that Arecoline triggers aberrant epithelium-fibroblast crosstalk and identified that epithelial cell-derived miR-17-5p mediates fibroblast differentiation through the classical TGF-ß fibrotic pathway, which provided a new perspective and strategy for the diagnosis and treatment of OSF.

METTL3 Promotes OSCC Progression by Down-Regulating WEE1 in a m6A-YTHDF2-Dependent Manner.

Oral squamous cell carcinoma (OSCC) is a common and highly lethal epithelial cancer. This study aimed to confirm the role of METTL3 in promoting OSCC and investigate its specific underlying mechanisms. Expression of the METTL3, YTH domain-containing family 2 (YTHDF2), and WEE1 were examined in normal oral epithelial cells and OSCC cells. Cell functions were examined after overexpressing WEE1 in OSCC cells. MeRIP-qPCR analysis was used to detect WEE1 m6A levels in HOK, SCC25, and CAL27 cells. WEE1 and its m6A levels were evaluated in OSCC cells by knocking down METTL3/YTHDF2, assessing the interaction between METTL3/YTHDF2 and WEE1. The impact of METTL3 and YTHDF2 downregulation on WEE1 mRNA stability was also investigated. The tumor weight and volume in a nude mouse model of OSCC after overexpression of WEE1 and YTHDF2 were measured. Expression of Ki-67 and WEE1 in OSCC tissue was detected using immunohistochemistry. Compared to normal oral epithelial cells, METTL3 and YTHDF2 were upregulated in OSCC cells, while WEE1 was downregulated, and there was a negative correlation between WEE1 and METTL3/YTHDF2 expression. WEE1 overexpression inhibited proliferation, invasion, and migration while promoting apoptosis in OSCC cells. METTL3 and YTHDF2 bound to WEE1 mRNA. METTL3/YTHDF2 knockdown increased WEE1 levels and WEE1 mRNA stability. METTL3 inhibition reduced WEE1 m6A levels. Inhibition of METTL3 weakened the interaction between YTHDF2 and WEE1 mRNA. In vivo, overexpression of WEE1 suppressed OSCC development, which was reversed by overexpression of YTHDF2. METTL3 facilitates the progression of OSCC through m6A-YTHDF2-dependent downregulation of WEE1.

The novel insights of epithelial-derived exosomes in various fibrotic diseases.

The characteristics of fibrosis include the abnormal accumulation of extracellular matrix proteins and abnormal tissue repair caused by injury, infection, and inflammation, leading to a significant increase in organ failure and mortality. Effective and precise treatments are urgently needed to halt and reverse the progression of fibrotic diseases. Exosomes are tiny vesicles derived from endosomes, spanning from 40 to 160 nanometers in diameter, which are expelled into the extracellular matrix environment by various cell types. They play a crucial role in facilitating cell-to-cell communication by transporting a variety of cargoes, including proteins, RNA, and DNA. Epithelial cells serve as the primary barrier against diverse external stimuli that precipitate fibrotic diseases. Numerous research suggests that exosomes from epithelial cells have a significant impact on several fibrotic diseases. An in-depth comprehension of the cellular and molecular mechanisms of epithelial cell-derived exosomes in fibrosis holds promise for advancing the exploration of novel diagnostic biomarkers and clinical drug targets. In this review, we expand upon the pathogenic mechanisms of epithelium-derived exosomes and highlight their role in the fibrotic process by inducing inflammation and activating fibroblasts. In addition, we are particularly interested in the bioactive molecules carried by epithelial-derived exosomes and their potential value in the diagnosis and treatment of fibrosis and delineate the clinical utility of exosomes as an emerging therapeutic modality, highlighting their potential application in addressing various medical conditions.

LACTB suppresses migration and invasion of glioblastoma via downregulating RHOC/Cofilin signaling pathway.

Glioblastoma (GBM) is the most malignant tumor in human brain. High invasiveness of this tumor is the main reason causing treatment failure and recurrence. Previous study has found that LACTB is a novel tumor suppressor in breast cancer. Moreover, the function of LACTB in other tumors and mechanisms involving LACTB were also reported. However, the role and relevant mechanisms of LACTB in GBM invasion remains to be revealed. Our aim is to investigate the role LACTB in GBM migration and invasion. We found that LACTB was downregulated in gliomas compared to normal brain tissues. Overexpression of LACTB suppressed migration and invasion of LN229 and U87 cell lines. Mechanistically, LACTB overexpression downregulated the mesenchymal markers. Moreover, LACTB overexpression downregulated the expression of RHOC and inhibited RHOC/Cofilin signaling pathway. The study suggests that LACTB suppresses migration and invasion of GBM cell lines via downregulating RHOC/Cofilin signaling pathway. These findings suggest that LACTB may be a potential treatment target of GBM.

The role of long noncoding RNAs as regulators of the epithelial-Mesenchymal transition process in oral squamous cell carcinoma cells.

Oral squamous cell carcinoma (OSCC) is a highly invasive and relatively prevalent cancer, accounting for around 3% of all cancers diagnosed. OSCC is associated with bad outcomes, with only 50% overall survival (OS) after five years. The ability of OSCC to invade local and distant tissues relies on the induction of the epithelial-mesenchymal transition (EMT), wherein epithelial cells shed their polarity and cell-to-cell contacts and acquire mesenchymal characteristics. Consequently, a comprehensive understanding of how tumor cell EMT induction is regulated has the potential of direct attempts to prevent tumor progression and metastasis, resulting in better patient outcomes. Several recent studies have established the significance of particular long noncoding RNAs (lncRNAs) in the context of EMT induction. Moreover, lncRNAs regulate a vast array of oncogenic pathways. With a focus on the mechanisms by which the underlined lncRNAs shape the metastatic process and a discussion of their potential utility as clinical biomarkers or targets for therapeutic intervention in patients with OSCC, the present review thus provides an overview of the EMT-related lncRNAs that are dysregulated in OSCC.

Bilateral aneurysms, one of which is embedded in a meningioma: a rare case report and literature review.

BACKGROUND: Although the coexistence of primary brain neoplasms with intracranial aneurysms is rare, this phenomenon has become more recognized. Meningioma is the most frequently occurring type of tumor associated with an aneurysm. However, meningiomas encasing aneurysms are extremely rare, posing a diagnostic and therapeutic challenge to healthcare providers. CASE DESCRIPTION: We report a case of a 46-year-old female patient admitted to our hospital with headache and dizziness for ten years. Enhanced magnetic resonance imaging (MRI) and magnetic resonance angiography (MRA) indicated a mass in the right sphenoid ridge, surrounding a posterior communicating artery aneurysm of the right internal carotid artery. Digital subtraction angiography (DSA) revealed left ophthalmic segment aneurysm and right posterior communicating artery aneurysm. We first clipped the aneurysm and then removed intracranial tumor during the same operation. The postoperative pathological diagnosis of tumor was meningioma (World Health Organization grade I). The patient's postoperative course was uneventful, with only a mild reduction in lateral vision of both eyes. CONCLUSIONS: We reported a rare case in which an intracranial aneurysm was encased in a meningioma and could be safely treated during the same operation. Notably, embolizing or clipping aneurysm first and then removing intracranial tumor appears to enhance the safety of patients. This is the best treatment option if the aneurysm and meningioma can be treated concurrently in the hybrid operating room. Additionally, it may be necessary to carefully evaluate preoperative MRA or computed tomography angiography (CTA), and it is critical to confirm the existence of any vascular lesions in patients with brain tumors using MRA or CTA.

Gamma Knife Radiosurgery for Cavernous Malformations of Basal Ganglia and Thalamus: A Retrospective Study of 53 Patients.

INTRODUCTION: Gamma Knife radiosurgery (GKRS) has been used to treat cavernous malformations (CMs) located in basal ganglia and thalamus. However, previous reports are limited by small patient population. METHODS: We retrospectively reviewed the clinical and radiological data of 53 patients with CMs of basal ganglia and thalamus who underwent GKRS at West China Hospital between May 2009 and July 2018. All patients suffered at least once bleeding before GKRS. The mean volume of these lesions was 1.77 cm3, and the mean marginal dose was 13.2 Gy. After treatment, patients were followed to determine the change in symptom and hemorrhage event. RESULTS: The mean follow-up period was 52.1 months (6.2-104.3 months). The calculated annual hemorrhage rate (AHR) was 48.5% prior to GKRS and 3.0% after treatment (p < 0.001). The Kaplan-Meier analysis revealed that 2-, 3-, and 5-year hemorrhage-free survival were 88, 80.9, and 80.9%, respectively. Preexisting symptoms were resolved in 11 patients, improved in 14, and stable in 5. Only 2 patients (3.8%) developed new neurological deficit. CONCLUSION: Our study suggests that AHR after GKRS was comparable to the recorded AHR of natural history (3.1-4.1%) in previous studies. GKRS is a safe and effective treatment modality for CMs of basal ganglia and thalamus. Considering the relative insufficient understanding of natural history of CMs, future study warrants longer follow-up.

Gamma Knife radiosurgery as the initial treatment for elderly patients with nonfunctioning pituitary adenomas.

PURPOSE: The aim of this study was to investigate the efficacy and safety of initial Gamma Knife radiosurgery (GKRS) for elderly patients with nonfunctioning pituitary adenomas (NFPAs). METHODS: We retrospectively reviewed 45 elderly patients underwent GKRS as the initial treatment for NFPAs at our institution between December 2007 and December 2017. Patients' radiographic and clinical data were collected. RESULTS: The median age of patients at the time of GKRS was 71 years (range 65-82 years). The median tumor volume was 2.6 cm3 (range 0.3-21.8 cm3). The median marginal dose was 13 Gy (range 6-23 Gy). The median maximum dose to the optic apparatus was 6.5 Gy (range 2.3-10.3 Gy). Thirty-five patients (77.8%) achieved tumor regression, 6 patients (13.3%) had tumor stable and 4 patients (8.9%) occurred tumor progression during a median radiological follow-up time of 51.4 months (range 11.1-158.7 months). The crude tumor control rate was 91.1%. The actuarial tumor control rates were 100%, 95.0%, 87.6%, and 87.6%, at 1, 3, 5, and 10 years after initial GKRS, respectively. New-onset hypopituitarism occurred in 6 patients. Two patients with pre-GKRS visual dysfunction developed further deterioration of visual function. No other radiation-induced complications were noted. CONCLUSION: Initial GKRS can provide a high tumor control rate as well as low risk of postradiosurgical complications for elderly patients with NFPAs. Attention should be paid to avoid radiation-related adverse effects including hypopituitarism, optic neuropathy and cranial neuropathy in elderly patients.

Oral submucous fibrosis transforming into squamous cell carcinoma: a prospective study over 31 years in mainland China.

OBJECTIVE: Oral submucous fibrosis (OSF) is an oral mucous disease caused by betel quid chewing. It is controversial whether OSF can transform into oral squamous cell carcinoma (OSCC). MATERIALS AND METHODS: In this prospective study, a group of 567 patients with OSF were enrolled from 1986 to 2017 and followed-up until 2019. The cancerous information was collected and analyzed. RESULTS: OSF transformed into OSCC in 32 cases (32/567, 5.6%). The patient's age ranged from 20 to 69 years, and the average age was 52 years. The time taken for transformation ranged from 2 to 24 years, the average being 8.6 years. The cancerous transformation occurred in 18 patients (56%) from years 2 to 9, in 13 patients (41%) from years 10-19 and in 1 patient (3%) from 24 years. We analyzed the betel quid chewing habits and found all 32 patients with OSCC-chewed betel quid. Betel quid chewing was most prevalent in patients aged 40-69 years. Sixteen patients had chewed betel quid for 10-19 years (16/32, 50%) and 19 patients (60%) chewed 10-19 slices each day. The OSCC was located in the left or right buccal regions in 23 patients (23/32; 72%) and in the left or right lingual regions in 4 patients (4/32; 12%). Well, moderately and poorly differentiated squamous cell carcinoma was present in 23 patients (23/32; 72%), 4 patients (3/32; 9%), and 5 patients (5/32; 16%), respectively. CONCLUSION: Our findings supported that OSF is a real oral premalignant disorder. CLINICAL RELEVANCE: The long duration of the transformation from the OSF to OSCC suggests more frequent examinations and corresponding treatments are necessary for OSF patients.

Differential expression of programmed death-1 and its ligand, programmed death ligand-1 in oral squamous cell carcinoma with and without oral submucous fibrosis.

OBJECTIVE: The aim of our study was to investigate the expression of programmed death ligand-1 (PD-L1)/programmed death-1 (PD-1) between oral squamous cell carcinoma (OSCC) patients with and without oral submucous fibrosis (OSF), and its correlation with clinic-pathologic features and its prognostic value. METHODS: PD-L1 and PD-1 expression was evaluated by immunohistochemical staining, double immunofluorescent staining and real-time PCR, and the correlation of PD-L1/PD-1 expression with clinical outcome was assessed. RESULTS: The level of PD-L1 expression was significantly higher in OSCC with OSF than in OSCC without OSF (p = 0.006). Moreover, PD-L1 expression was strongly correlated with lymph node metastasis (p = 0.016), and advanced tumor stage (p = 0.030). Increased PD-L1 expression was positively correlated with the incidence of OSCC with OSF (p = 0.006, p = 0.008, respectively). PD-L1 expression was an independent marker of unfavorable prognosis (p = 0.035, p = 0.048, respectively). High PD-L1 expression had a significantly worse outcome in OSCC patients with OSF (p = 0.014). Double immunofluorescent staining showed that OSCC with OSF were more strongly expressed both PD-L1 and PD-1 than OSCC without OSF. Moreover, the expression of PD-L1 were upregulated in OSCC tissues than normal control (p = 0.0422), and both PD-L1 and PD-1 was significantly higher in OSCC with OSF than OSCC without OSF tissues (p = 0.0043 and, p = 0.0012, respectively). CONCLUSIONS: The present study suggested that PD-L1 may be an unfavorable indicator for prognosis. PD-L1/PD-1 signaling might play an important role in the malignant transformation of OSF, and targeting PD-L1/PD-1 signaling may be a new therapeutic strategy for OSCC, especially in OSCC patients with OSF.

Pre-stereotactic radiosurgery neutrophil-to-lymphocyte ratio is a predictor of the prognosis for brain metastases.

PURPOSE: The neutrophil-to-lymphocyte ratio (NLR) has been reported to relate to the prognosis of various cancers. The aim of this study was to elucidate the efficiency of pre-treatment NLR as a predictor of outcomes of brain metastasis underwent gamma knife radiosurgery (GKRS). METHODS: We analyzed 195 cases with brain metastasis underwent GKRS at our institution between January 2015 and April 2018. Patients' clinical and radiographic data were collected. RESULTS: We identified 458 brain metastases in 195 patients. Optimal dichotomous cutoff values of NLR determined by receiver operating characteristic analysis for local control, distant control and overall survival (OS) were 2.48, 2.74 and 3.13, respectively. The actuarial local control rates of patients with high NLR were 87.4% at 6 months and 76.1% at 12 months, whereas that of patients with low NLR were 94.2% at 6 months and 88.3% at 12 months (P = 0.001). The actuarial distant control rates of patients with high NLR were 31.4% at 6 months and 18.9% at 12 months, whereas that of patients with low NLR were 58.5% at 6 months and 31.3% at 12 months (P = 0.001). The median OS of patients with high and low NLR were 10.0 months and 14.5 months, respectively (P = 0.001). Multivariate analysis demonstrates that high NLR independently predicts local failure (hazard ratio [HR], 2.281; P = 0.003), distant brain failure (HR 1.775; P = 0.002) and poorer overall survival (HR 1.494; P = 0.034). CONCLUSION: The pre-SRS NLR, a systemic inflammatory marker for treatment response, inversely predicts local control, distant control and OS in patients with brain metastasis.

Comparison of clinical outcomes in patients who underwent Gamma Knife radiosurgery for parasellar meningiomas with or without prior surgery.

BACKGROUND: Parasellar meningioma is a common benign tumour in brain. Both surgery and radiosurgery are important treatment modalities for this tumour. The study was designed to investigate whether prior surgery would affect treatment outcomes of patients with parasellar meningiomas after management with Gamma Knife radiosurgery. METHODS: A total of 93 patients who received Gamma Knife surgery were included in this retrospective study. There were 30 males and 63 females, with a median age of 48.6 years (range, 15.2-78.7 years). Prior surgery was performed in 45 patients. The median tumor volume was 5.02 cm3 (range 1.07-35.46 cm3) and median marginal dose was 12 Gy (range 10-15 Gy). The mean imaging follow-up and clinical follow-up periods were 40.7 and 52.7 months, respectively. RESULTS: In the group without prior surgery, 31 patients had improvement of preexisting symptoms; and in the group with prior surgery, 20 patients were noted to improve. The difference in symptom improvement between the two groups reached statistical significance (P = 0.009). Patients with prior surgery were more likely to have stable symptoms after Gamma Knife surgery (P = 0.012). Tumor recurrence was reported in 8 patients out of 45 patients with prior surgery, and 3 patients out of 48 patents without prior surgery (P = 0.085). After Gamma Knife surgery, 5 and 4 patients in two groups developed new neurological symptoms, respectively (P = 0.651). Cox regression analysis identified follow-up period as prognostic factor of progression-free survival. Ordinal logistic regression analysis identified surgery prior to Gamma Knife surgery as an unfavorable factor of symptom change. CONCLUSION: Gamma Knife radiosurgery provided long-term effective tumor control and better symptom recovery compared with those with prior surgery. Patients with surgery before Gamma Knife radiosurgery were more likely to have stable symptoms. Further analyses indicated that long follow-up is essential to determine the efficacy of radiosurgery for parasellar meningiomas. Further study needs to include more patients with longer follow-up to draw a more solid conclusion.

Repertoire of peripheral T cells in patients with oral squamous cell carcinoma.

BACKGROUND: The establishment of adaptive immune responses to neoplasms involves not only the tumour tissue, but also the peripheral blood. We aimed to conduct a preliminary exploration to understand the immune response of T lymphocytes of peripheral blood mononuclear cells (PBMC-Ts) in oral squamous cell carcinoma (OSCC). METHODS: A total of 103 blood samples from OSCC patients and 18 blood samples from healthy donors (HD) were analysed by flow cytometry. RESULTS: Compared to those in HD, a series of unique features of PBMC-Ts were observed in OSCC patients including a significant increase in CD4+ T cells, a shift from naïve to memory/effector phenotype, an increased frequency of exhausted phenotypes (programmed death-1 [PD-1], T cell Ig and mucin protein-3 [Tim-3] and Tregs), an abundance of Th17s and Tc17s and an imbalance in Th17/Tc17 and Th17/Treg ratios. Furthermore, in OSCC patients, we also found that CD4+ T cells were significantly increased in patients with larger tumours than smaller tumours, memory/effector phenotype and exhausted phenotypes were significantly associated with advanced clinical stage and lymph node metastasis, and the Th17/Treg ratio was associated with early clinical stage and no lymph node metastasis. CONCLUSION: PBMC-Ts may be involved in the development and progression of OSCC, which suggested to be a manifestation of an immune response between host and tumour neoantigens.

The repertoire of tumor-infiltrating lymphocytes within the microenvironment of oral squamous cell carcinoma reveals immune dysfunction.

BACKGROUND: The role of tumor-infiltrating lymphocytes (TILs) in the immune remodeling of tumor microenvironments (TME) in oral squamous cell carcinoma (OSCC) remains controversial. In this study, we pursued a comprehensive characterization of the repertoire of TILs and then analyzed its clinical significance and potential prognostic value. METHODS: Fresh tumor tissue samples and peripheral blood from 83 OSCC patients were collected to comprehensively characterize the phenotypes and frequencies of TILs by flow cytometry. Archived paraffin-embedded tissues derived from 159 OSCC patients were analyzed by immunohistochemistry to further assess the TIL repertoire. The clinical significance of TILs and their potential prognostic value were further analyzed. RESULTS: A series of unique features of TILs were observed. IL-17 was highly expressed in betel nut chewers, and CD20 was abundantly expressed in patients who did not drink alcohol; high expression of CD138, PD-L1, and Foxp3 was associated with poor prognosis. The Th17/Treg ratio was an independent prognostic factor for patient survival with greater predictive accuracy for overall survival. CONCLUSIONS: Our results suggest an antigen-driven immune response; however, the immune dysfunction within the microenvironment in OSCC and the Th17/Treg balance may play important roles in the modulation of antitumor immunity.

Efficacy and Safety of Hypofractionated Stereotactic Radiotherapy for Recurrent Malignant Gliomas: A Systematic Review and Meta-analysis.

BACKGROUND: The current treatment for patients with relapsed malignant glioma (MG) remains unsatisfactory. Use of hypofractionated stereotactic radiotherapy (HFSRT) for recurrent MG has shown some encouraging results and may be a viable option. METHODS: We performed a systematic review and meta-analysis of articles that investigated the use of HFSRT for recurrent MG. Relevant studies were obtained through searching PubMed, Embase, and the Cochrane Library. Data about treatment regimens, median overall survival, and radiation necrosis (RN), as well as other major neurologic complications were extracted. We performed a descriptive analysis of the median overall survival and meta-analysis of the reported rates of RN and other major neurologic complications (MNCs). RESULTS: A total of 26 studies were included in our study, comprising 861 patients. Median overall survival ranged from 8.6 to 18 months. A total of 19 studies were included to perform a meta-analysis of the RN rate and the pooled RN rate was 5% (3%-7%). The pooled rate of other MNCs was 2% (1%-4%), calculated from 20 studies. CONCLUSIONS: The present evidence suggests that HFSRT is an efficacious and safe treatment approach to treat patients with recurrent MG. However, the retrospective and observational nature of the studies included in our systematic review and meta-analysis restricted formation of more solid conclusions. Thus, well-designed prospective controlled trials are warranted to further define the therapeutic role of HFSRT for recurrent MG.

H19/miR-30a/C8orf4 axis modulates the adipogenic differentiation process in human adipose tissue-derived mesenchymal stem cells.

The adipogenic differentiation of adipose tissue-derived mesenchymal stem cells (ADSCs) is a critical issue in many obesity-related disorders. Cytidine-cytidine-adenosine-adenosine-thymidine (CCAAT) enhancer binding protein α (CEBP-α) and peroxisome proliferator-activated receptor-γ are two important lipogenic and adipogenic transcription factors and markers in adipogenic differentiation. Noncoding RNAs participate in adipogenic differentiation. The long noncoding RNA (lncRNA) H19 is related to multiple cellular differentiation, including adipogenic differentiation; however, its function and precise molecular mechanism in human ADSCs (hADSCs) adipogenic differentiation are unclear. microRNAs that were differentially expressed in adipogenic differentiation and could be targeted by H19 were screened and selected; the regulation and interaction between H19 and miR-30a were verified. The interaction between miR-30a and predicted downstream target C8orf4 was validated. The dynamic effects of H19 and miR-30a on C8orf4 messenger RNA (mRNA) expression and protein and adipogenic differentiation were evaluated. miR-30a negatively regulated H19 with each other through direct binding. As predicted by TargetScan and verified using luciferase reporter gene assays, miR-30a directly bound to the 3'-untranslated region of C8orf4 to inhibit its expression; H19 knockdown suppressed while miR-30a inhibition promoted the mRNA expression and the protein levels of C8orf4 and adipogenic differentiation; the effect of H19 knockdown could be partially reversed by miR-30a inhibition. The lncRNA H19 serves as a competing endogenous RNA (ceRNA) for miR-30a to augment miR-30a downstream target C8orf4, therefore modulating adipogenic differentiation in hADSCs. From the perspective of lncRNA-miRNA-mRNA regulation, we provided a novel regulatory mechanism of hADSCs adipogenic differentiation.

[Anterolateral thigh flap for reconstruction of defects after en bloc resection of buccal cancer : a retrospective study of 23 cases].

PURPOSE: This study was aimed to observe the effects of anterolateral thigh flap for reconstruction of tissue defects after en bloc resection of buccal cancer. METHODS: Twenty-three patients with soft tissue defects after en bloc resection of buccal cancer underwent simultaneous reconstruction with anterolateral thigh flap from May, 2013 to May, 2015 were observed. Anterolateral thigh flaps were designed and harvested in form of single or multiple islands to restore the defect in buccal region after surgery. The appearance and function of both the oral and maxillofacial region and the donor site were recorded and evaluated. RESULTS: All the 23 flaps survived. Only 3 of them experienced vascular crisis within 24 hours after surgery, and recovered gradually after salvage. The success rate was 100%. One to three years of follow-up showed satisfying morphology and function for both the receipt sites and the donor sites. Buccal abscess was observed in 1 patient and recovered after rinsing and drainage. Two patients died of recurrence. CONCLUSIONS: Good effects can be achieved using anterolateral thigh flap to reconstruct buccal defects after en bloc resection of cancer, which is suitable for application in clinical practice.