Hypoxia-responsive circular RNA circAAGAB reduces breast cancer malignancy by activating p38 MAPK and sponging miR-378 h.

BACKGROUND: Breast cancer is a prevalent disease in women, with high prevalence worldwide. The hypoxic microenvironment of solid tumors develops during the progress of carcinogenesis and leads to greater malignancy and treatment resistance. Recently, accumulating evidence indicates that non-coding RNAs, such as circular RNAs (circRNAs), play a pivotal role in altering cellular functions. However, the underlying mechanisms of circRNAs in breast cancer are still unclear. Therefore, the purpose of this study was to investigate the role of a tumor-suppressive circRNA, circAAGAB, in breast cancer by assuming down-regulation of circAAGAB under hypoxia and the properties of a tumor suppressor. METHODS: Firstly, circAAGAB was identified from expression profiling by next generation sequencing. Next, the stability of circAAGAB increased by interacting with the RNA binding protein FUS. Moreover, cellular and nuclear fractionation showed that most circAAGAB resided in the cytoplasm and that it up-regulated KIAA1522, NKX3-1, and JADE3 by sponging miR-378 h. Lastly, the functions of circAAGAB were explored by identifying its down-stream genes using Affymetrix microarrays and validated by in vitro assays. RESULTS: The results showed that circAAGAB reduced cell colony formation, cell migration, and signaling through p38 MAPK pathway, as well as increased radiosensitivity. CONCLUSION: These findings suggest that the oxygen-responsive circAAGAB acts as a tumor suppressor in breast cancer, and may contribute to the development of a more specific therapeutic regimen for breast cancer.

Changes in arthropod community but not plant quality benefit a specialist herbivore on plants under reduced water availability.

Plants growing under reduced water availability can affect insect herbivores differently, in some instances benefitting them. However, the forces mediating these positive impacts remain mostly unclear. To identify how water availability impacts plant quality and multi-trophic interactions, we conducted manipulative field studies with two populations of the specialist herbivore Pieris rapae, and its host plant, Rorippa indica. We found that P. rapae larvae experienced higher survival on R. indica growing under low water availability compared with plants grown under high water availability. Higher survival of eggs and larvae was related to the reduced abundance of other herbivores and natural enemies. Water availability had differential impacts on other members of the herbivore community by altering plant quality. Low water availability decreased the quality of R. indica to most herbivores, as indicated by reduced abundance in the field and decreased relative growth rate in laboratory feeding assays. In contrast, P. rapae larval performance was not affected by sympatric R. indica grown under different water availability. These results indicate that local P. rapae populations possess physiological adaptations to overcome fluctuations in host quality. Our findings illustrate that reduced water availability is beneficial to a specialist herbivore but detrimental to most other herbivores. Our work highlights the complex effects of the arthropod communities associated with plants in determining the impacts of water availability on insect herbivores.

Er:YAG laser promotes proliferation and wound healing capacity of human periodontal ligament fibroblasts through Galectin-7 induction.

BACKGROUND/PURPOSE: Among various dental lasers, the erbium-doped yttrium-aluminum-garnet (Er:YAG) laser has great potential for periodontal treatment including soft and hard tissue ablation with minimal thermal side effects under suitable energy densities and it has multiple effects on tissues for wound-healing benefits. In the present study, we sought to reveal the molecular mechanism underlying the impact of Er:YAG laser on PDL fibroblasts. METHODS: Cells were irradiated by a Er:YAG laser with various energy densities (3.6-6.3 J/cm2). MTT assay was used for cell proliferation, and the transwell system was employed for migration and invasion abilities. The wound healing capacity was evaluated by a scratch assay. After confirming these effects, qRT-PCR and western blotting analysis was applied to identify the differentially galectin-7 expression in the irradiated cells. Knockdown experiments were conducted to reveal the functional role of galectin-7 in the modulation of Er:YAG laser-mediated effects. RESULTS: 4.2 J/cm2 was the lowest energy density to induce the optimal cell proliferation, migration and invasion abilities. In the group of upregulated genes, galectin-7 was selected for further examination and its elevation after Er:YAG laser treatment was validated by RT-PCR and Western blot. We demonstrated that silence of galectin-7 abrogated the effects of Er:YAG laser on cell proliferation, migration ad invasion, suggesting the Er:YAG laser promoted these effects through induction of galectin-7. CONCLUSION: These findings indicated that Er:YAG laser may accelerate the regeneration process in periodontal tissues through enhancement of their proliferative and mobile activities. Additionally, the significance of galectin-7 in the Er:YAG laser-elicited benefits was demonstrated.

Magnolol ameliorates the accumulation of reactive oxidative stress and inflammation in diabetic periodontitis.

BACKGROUND/PURPOSE: Periodontal disease and diabetes mellitus (DM) are both chronic inflammatory and highly prevalent diseases. A large amount of evidence suggested that the accumulation of oxidative stress plays a significant role in the deterioration of both diseases. Magnolol has been known to possess anti-inflammatory and anti-oxidant activities in various tissues, but its effects on gingival cells under diabetic conditions have not been fully understood. METHODS: We assessed the generation of reactive oxygen species (ROS), Transwell migration, and wound healing ability in response to the advanced glycation end products (AGEs) stimulation with or without Magnolol treatment. Subsequently, we examined the expression of Nrf2 and HO-1 to ascertain whether Magnolol was able to activate the anti-oxidant signaling. We also measured the secretion of IL-6 and IL-8, and conducted a knockdown experiment to elucidate the effect of Mrf2 on their secretion. RESULTS: The AGEs-induced ROS was dose-dependently downregulated following the Magnolol treatment. Likewise, the reduced Transwell migration and wound healing ability were improved by various concentrations of Magnolol. Results from qRT-PCR indicated that the suppression of Nrf2 and HO-1 following AGEs stimulation was reversed by Magnolol. Also, the AGEs-elicited production of IL-6 and IL-8 was inhibited by Magnolol. Moreover, our results demonstrated that this anti-inflammatory effect was mediated by the upregulation of Nrf2. CONCLUSION: These findings showed that excessive AGEs in the gingiva may lead to the accumulation of ROS and pro-inflammatory cytokines. Supplement of Magnolol may be beneficial to improve the impaired wound healing and inflammation by upregulation of Nrf2 signaling for DM patients with periodontal disease.

Inhibition of HIF1A-AS1 impedes the arecoline-induced migration activity of human oral mucosal fibroblasts.

Long non-coding RNA hypoxia-inducible factor 1α-antisense RNA 1 (HIF1A-AS1) has been known to participate in various types of malignancies, but its role in the development of precancerous oral submucous fibrosis (OSF) has not been investigated. In the current study, we first observed the aberrant upregulation of HIF1A-AS1 in OSF tissues and fibrotic buccal mucosal fibroblasts (fBMFs) isolated from OSF specimens. Next, we demonstrated that administration of arecoline, a natural alkaloid that is found in areca nut, induced the elevation of HIF1A-AS1 in BMFs. This finding showed that the habit of areca nut chewing may lead to an increase of HIF1A-AS1 in oral mucosa. Moreover, we found that knockdown of HIF1A-AS1 hindered the arecoline-stimulated migration capacity in BMFs, suggesting HIF1A-AS1 was critical to the transdifferentiation of BMFs into myofibroblasts. Altogether, our results demonstrated that overexpression of HIF1A-AS1 in OSF tissues may result from the use of areca nut and lead to activation of BMFs, which contribute to the progression of OSF.

E3 ligase STUB1 attenuates stemness and tumorigenicity of oral carcinoma cells via transglutaminase 2 regulation.

BACKGROUND/PURPOSE: Oral cancer is amongst the most prevalent cancers worldwide with rising incidence. Various attempts have been made to elucidate its pathogenesis, and we sought to examine the function of a ubiquitin E3 ligase that was encoded by STUB1. METHODS: The mRNA expression of STUB1 in oral cancer samples and normal counterparts was determined by qRT-PCR. Numerous assays to assess the features of cancer cells, including self-renewal capacity, invasion and migration abilities were conducted following knockdown or overexpression of STUB1. RESULTS: The expression level of STUB1 was reduced in oral cancer, which was associated with a reduced relapse-free survival. Two oral cancer cell lines with low expression of STUB1 (SAS and HSC3) were chosen for the overexpression of STUB1. We showed that ectopic expression of STUB1 led to the downregulation of TGM2, a multifunctional protein that contributed to cancer progression in several cancers. Our results demonstrated that overexpression of STUB1 suppressed the cancer aggressiveness, while restoration of TGM2 reverted the effects. Last, we showed that STUB1 silencing resulted in enhanced cancer features. CONCLUSION: The abnormal downregulation of STUB1 may lessen its suppressive effect on TGM2, which induced the onset or exacerbated the progression of oral cancer. The therapeutic approach to enhance the expression of STUB1 could be a promising direction for cancer therapy.

E3 ligase carboxyl-terminus of Hsp70-interacting protein (CHIP) suppresses fibrotic properties in oral mucosa.

BACKGROUND/PURPOSE: Oral submucous fibrosis (OSF) represents a precancerous lesion of oral mucosa that may progress into oral cancer and its major etiological factor is areca nut chewing. Carboxyl-terminus of Hsp70-interacting protein (CHIP) functions as an ubiquitin E3 ligase and is associated with fibrosis diseases. In the current study, we sought to investigate whether CHIP participated in the areca nut-mediated OSF development. METHODS: The mRNA expression of CHIP in arecoline-stimulated buccal mucosal fibroblasts (BMFs) and OSF tissues was determined by qRT-PCR. Collagen gel contraction, migration and invasion assays were carried out to evaluate the myofibroblast activation. The protein expression levels of α-SMA and transglutaminase 2 (TGM2) were assessed by Western blot. RESULTS: The expression level of CHIP was reduced in BMFs following arecoline treatment in a dose-dependent manner, which was consistent with the observation of lower CHIP expression in OSF specimen compared to the normal counterparts. Ectopic expression of CHIP mitigated the myofibroblast activities, including elevated collagen gel contractility and cell motility. In addition, we showed that overexpression of CHIP downregulated the α-SMA and TGM-2 expression, which may lead to less fibrosis alteration. CONCLUSION: CHIP may not only function as a key regulator of protein quality control but also a critical deciding factor to oral fibrogenesis. Our findings suggested that CHIP possesses the anti-fibrotic effect, which may be mediated by TGM2 regulation. Restoration of CHIP could be a therapeutic direction to help OSF patients.

miR-200a inhibits proliferation rate in drug-induced gingival overgrowth through targeting ZEB2.

BACKGROUND/PURPOSE: Gingival overgrowth can occur as a result of poor oral hygiene or a side effect of taking certain medications, such as cyclosporine A (CsA). It has been shown that this immunosuppressant drug induces epithelial-to-mesenchymal transition (EMT) in the gingival epithelium but the associated molecular mechanism remains to be elucidated. METHODS: We first assessed the relative expression of microRNA-200a (miR-200a) in response to the CsA treatment using qRT-PCR. Next, luciferase reporter assay was applied to examine whether miR-200a was able to regulate ZEB2 and Western blot was utilized to measure the expression of ZEB2 in normal human gingival fibroblasts (HGFs). To confirm the significance of miR-200a and ZEB2 in the CsA-induced gingival overgrowth, miR-200a inhibitor and shRNA mediated knockdown of ZEB2 were used and cell proliferation in HGFs was assessed by MTT assay. RESULTS: The expression of miR-200a was dose-dependently downregulated following the CsA treatment. Luciferase reporter assay confirmed that ZEB2 was a direct downstream target regulated by miR-200a and ZEB2 was indeed increased after the administration of CsA. We demonstrated that knockdown of ZEB2 hampered the CsA-induced HGFs proliferation and the elevated cell proliferation due to inhibition of miR-200a was reversed by repression of ZEB2. CONCLUSION: Our results showed that insufficient miR-200a in HGFs caused by CsA administration may lead to gingival enlargement mediated by the upregulation of ZEB2. This finding supported that CsA-induced EMT contributed to the adverse effect of using CsA and miR-200a may serve as an upstream target to prevent the overgrowth of the gingiva.

Synergistic Effects of Volatiles from Host-Infested Plants on Host-Searching Behavior in the Parasitoid Wasp Lytopylus rufipes (Hymenoptera: Braconidae).

Herbivore-induced plant volatiles (HIPVs) are important cues for natural enemies to find their hosts. HIPVs are usually present as blends and the effects of combinations of individual components are less studied. Here, we investigated plant volatiles in a tritrophic system, comprising the parasitoid wasp Lytopylus rufipes Nees (Hymenoptera: Braconidae), the Oriental fruit moth Grapholita molesta (Busck) (Lepidoptera: Tortricidae), and Japanese pear, Pyrus pyrifolia 'Kosui', so as to elucidate the effects of single components and blends on wasp behaviors. Bioassays in a four-arm olfactometer, using either shoots or their isolated volatiles collected on adsorbent, revealed that female wasps preferred volatiles from host-infested shoots over those from intact shoots. Analyses identified (Z)-3-hexenyl acetate (H), linalool (L), (E)-ß-ocimene (O), (E)-3,8-dimethyl-1,4,7-nonatriene (D), and (E,E)-α-farnesene (F). Among them, only F was induced by infestation with G. molesta. When tested singly, only O and D elicited positive responses by L. rufipes. Binary blends of HO and DF elicited a positive response, but that of HD elicited a negative one, even though D alone elicited a positive response. Remarkably, wasps did not prefer either the ODF or HL blends, but showed a highest positive response to a quinary blend (HLODF). These results show that synergism among volatiles released from host-infested plants is necessary for eliciting high behavioral responses in L. rufipes, enabling L. rufipes to find its host efficiently.

miR-1246 as a therapeutic target in oral submucosa fibrosis pathogenesis.

BACKGROUND/PURPOSE: Oral submucous fibrosis (OSF) is a precancerous condition of oral cancer with a complex etiology. Our previous work has demonstrated that non-coding RNA miR-1246 contributes to the cancer stemness of oral cancer. In the current study, we sought to investigate the effect of the inhibition of miR-1246 on the oral fibrogenesis. METHODS: The expression levels of miR-1246 in OSF tissues and fibrotic buccal mucosal fibroblasts (fBMFs) were examined by qRT-PCR. Collagen gel contraction and migration assays were conducted to evaluate the myofibroblast activities. The relationship between miR-1246 and type I collagen was assessed and the protein expression of type I collagen was determined by Western blot. RESULTS: MiR-1246 expression was upregulated in both OSF specimen and fBMFs compared to the normal counterparts. Inhibition of miR-1246 successfully suppressed the myofibroblast activities, including collagen gel contractility and migration capacity. Moreover, the expression of miR-1246 was positively correlated with type I collagen and the expression of type I collagen was abrogated by repression of miR-1246. CONCLUSION: MiR-1246 is not only critical to the maintenance of oral stemness but also important to the activation of myofibroblasts. Our results showed that miR-1246 is positively associated with the type I collagen, which may be a downstream effector of miR-1246 and responsible for the fibrosis effect on fBMFs.

Chemosensitizing effect of honokiol in oral carcinoma stem cells via regulation of IL-6/Stat3 signaling.

Oral squamous cell carcinoma (OSCC) is one of the most common cancers worldwide with poor prognosis. Numerous studies have attempted to explore alternative regimens aimed at reducing cancer stem cells (CSCs) without compromising the efficacy of conventional chemoradiotherapy. The present study sought to assess the effect of a natural compound honokiol on the reduction of elevated cancer stemness, metastatic capacity, and chemoresistance of oral carcinoma stem cells (OCSCs). Our results demonstrated that honokiol attenuated the cell survival and self-renewal of OCSCs in a dose-dependent manner. Moreover, honokiol downregulated the expression of 2 selective markers of OCSCs, ALDH1, and CD44, as well as the migration and invasion abilities, indicating its potential to suppress cancer stemness. We showed that honokiol reduced the secretion of IL-6 and phosphorylation of STAT3, and the honokiol-inhibited self-renewal, invasion and colony formation were reversed by administration of IL-6. Most importantly, our data demonstrated that honokiol was able to potentiate the effect of Cisplatin, leading to a lower proportion of OCSCs and the decreased cancer stemness features. Taken together, this study demonstrated the benefits of utilizing honokiol as an adjunct therapy for OSCC treatment.

Sulforaphane targets cancer stemness and tumor initiating properties in oral squamous cell carcinomas via miR-200c induction.

BACKGROUND/PURPOSE: Cancer stem cells (CSCs) are deemed as the driving force of tumorigenesis in oral squamous cell carcinomas (OSCCs). In this study, we investigated the chemotherapeutic effect of sulforaphane, a dietary component from broccoli sprouts, on targeting OSCC-CSCs. METHODS: The effect of sulforaphane on normal oral epithelial cells (SG) and sphere-forming OSCC-CSCs isolated from SAS and GNM cells was examined. ALDH1 activity and CD44 positivity of OSCC-CSCs with sulforaphane treatment was assessed by flow cytometry analysis. In vitro and in vivo tumorigenicity assays of OSCC-CSCs with sulforaphane treatment were presented. RESULTS: We observed that the sulforaphane dose-dependently eliminated the proliferation rate of OSCC-CSCs, whereas the inhibition on SG cells proliferation was limited. Cancer stemness properties including self-renewal, CD44 positivity, and ALDH1 activity were also decreased in OSCC-CSCs with different doses of sulforaphane treatment. Moreover, sulforaphane treatment of OSCC-CSCs decreased the migration, invasion, clonogenicity, and in vivo tumorigenicity of xenograghts. Sulforaphane treatment resulted in a dose-dependent increase in the levels of tumor suppressive miR200c. CONCLUSION: These lines of evidence suggest that sulforaphane can suppress the cancer stemness and tumor-initiating properties in OSCC-CSCs both in vitro and in vivo.

Au nanostructure-decorated TiO2 nanowires exhibiting photoactivity across entire UV-visible region for photoelectrochemical water splitting.

Here we demonstrate that the photoactivity of Au-decorated TiO2 electrodes for photoelectrochemical water oxidation can be effectively enhanced in the entire UV-visible region from 300 to 800 nm by manipulating the shape of the decorated Au nanostructures. The samples were prepared by carefully depositing Au nanoparticles (NPs), Au nanorods (NRs), and a mixture of Au NPs and NRs on the surface of TiO2 nanowire arrays. As compared with bare TiO2, Au NP-decorated TiO2 nanowire electrodes exhibited significantly enhanced photoactivity in both the UV and visible regions. For Au NR-decorated TiO2 electrodes, the photoactivity enhancement was, however, observed in the visible region only, with the largest photocurrent generation achieved at 710 nm. Significantly, TiO2 nanowires deposited with a mixture of Au NPs and NRs showed enhanced photoactivity in the entire UV-visible region. Monochromatic incident photon-to-electron conversion efficiency measurements indicated that excitation of surface plasmon resonance of Au is responsible for the enhanced photoactivity of Au nanostructure-decorated TiO2 nanowires. Photovoltage experiment showed that the enhanced photoactivity of Au NP-decorated TiO2 in the UV region was attributable to the effective surface passivation of Au NPs. Furthermore, 3D finite-difference time domain simulation was performed to investigate the electrical field amplification at the interface between Au nanostructures and TiO2 upon SPR excitation. The results suggested that the enhanced photoactivity of Au NP-decorated TiO2 in the UV region was partially due to the increased optical absorption of TiO2 associated with SPR electrical field amplification. The current study could provide a new paradigm for designing plasmonic metal/semiconductor composite systems to effectively harvest the entire UV-visible light for solar fuel production.

Er:YAG laser suppresses pro-inflammatory cytokines expression and inflammasome in human periodontal ligament fibroblasts with Porphyromonas gingivalis-lipopolysaccharide stimulation.

Background/purpose: Periodontitis is an inflammatory condition of the tooth-supporting structures triggered by the host's immune response towards the bacterial deposits around the teeth. It is well acknowledged that pro-inflammatory interleukin (IL)-6, IL-8, MCP-1 as well as the NOD-like receptor family pyrin domain containing 3 (NLRP3) inflammasome, are the key modulators in the activation of this response. Erbium-doped yttrium-aluminium-garnet (Er:YAG) laser, a solid-state crystal laser have been commonly used in the treatment of periodontal diseases. However, little is understood about the molecular mechanism of the Er:YAG laser, especially in targeting the host immune response brought on by periodontal pathogens. Hence, the current study focused on the protective effects of Er:YAG laser on periodontitis in-vitro in terms of pro-inflammatory cytokines, chemokines and NLRP3 inflammasome expressions. Materials and methods: Human periodontal ligament fibroblast (PDLFs) were first stimulated with lipopolysaccharides (LPS) from P. gingivalis (Pg-LPS) to simulate periodontitis. Cells were then irradiated with Er:YAG laser of ascending energy densities (3.6-6.3 J/cm2), followed by cell proliferation and wound healing assay. Next, the effects of Er:YAG laser on the expressions of IL-6, IL-8, MCP-1, NLRP3, and cleaved GSDMD were examined. Results: Pg-LPS was found to reduce cell's proliferation rate and wound healing ability in PDLFs and these were rescued by Er:YAG laser irradiation. In addition, LPS stimuli resulted in a marked upregulation in the secretion of IL-6, IL-8 and MCP-1 as well as the mRNA and protein expression of NLRP3 and cleaved-GSDMD protein whereas Er:YAG laser suppressed the elicited phenomena. Conclusion: To our knowledge, this is the first study to look into the laser's implication on the NLRP3 inflammasome in periodontitis models. Our study reveals a crucial role of Er:YAG laser in ameliorating periodontitis in-vitro through the modulation of IL-6, IL-8, MCP-1 and the NLRP3 inflammasome and highlights that the control of the NLRP3 inflammasome may become a potential approach for periodontitis.

Analysis of approved dental teaching projects in the teaching practice research program in 8 dental schools of Taiwan from 2018 to 2023.

Background/purpose: The teaching practice research program was initiated by Taiwan's Ministry of Education in 2018 to improve medical teaching quality. This study analyzed dental teaching projects conducted under this program from 2018 to 2023. Materials and methods: Data of submitted and approved medical (including dental) teaching projects from 2018 to 2023 were obtained from the annual reports released by the program committee. The annual passing rates were calculated by dividing the number of approved dental teaching projects by the total number of approved medical teaching projects in the category of medical and healthcare sciences in a particular year. The 24 approved dental teaching projects were reviewed, classified into different topics in the dental field, and then reported. Results: There were 24 approved dental teaching projects out of a total of 822 approved medical teaching projects from 2018 to 2023. The annual passing rates increased gradually from 2018 (1.4 %) to 2022 (3.9 %) and 2023 (3.8 %) with an overall mean passing rate of 2.9 % over a period of 6 years. Of the 24 approved dental teaching projects, digital dentistry was the most common teaching research topic (9 projects), followed by new teaching models (7 projects), 3D technology (3 projects), endodontics (3 projects), dental histology (one project), and evidence-based method (one project). Conclusion: Digital dentistry and new teaching models were the two predominant dental teaching research topics, suggesting that both are the modern trends in the dental education. However, the dental teaching research projects are still very limited in 8 Taiwanese dental schools.

Gastric adenocarcinoma predictive long intergenic noncoding RNA (GAPLINC) promotes oral cancer stemness by acting as a molecular sponge of miR331-3p.

Background/purpose: Accumulating evidence has suggested that treatment failure of cancer therapy can be attributed to cancer stem cells (CSCs). Among numerous regulators of cancer stemness, non-coding RNAs (ncRNAs) have gained significant attention recently. In this study, we examined the role of gastric adenocarcinoma predictive long intergenic noncoding RNA (GAPLINC) in oral CSCs (OCSCs). Materials and methods: RNA Sequencing and quantitative real-time polymerase chain reaction (qRT-PCR) were used to determine the expression of GAPLINC. Flow cytometry and sphere-forming assay were exploited to isolate OCSCs. Measurement of aldehyde dehydrogenase 1 (ALDH1) activity, CD44 expressing cells, and various phenotypic assays, such as self-renewal, migration, invasion, and colony-forming abilities, were conducted in CSCs of two types of oral cancer cells (SAS and GNM) following the knockdown of GAPLINC. A luciferase reporter was also carried out to validate the direct interaction between GAPLINC and microRNA (miR)-331-3p. Results: Our results showed that GAPLINC was overexpressed in OCSCs from patient-derived and oral cancer cell lines. We demonstrated that silencing of GAPLINC in OCSCs downregulated various CSC hallmarks, such as ALDH1 activity, percentage of CD44-expressing cells, self-renewal capacity, and colony-forming ability. Moreover, our results revealed that the effect of GAPLINC on cancer stemness was mediated by direct repression of miR-331-3p. Conclusion: These data have potential clinical implications in that we unraveled the aberrant upregulation of GAPLINC and demonstrated that suppression of GAPLINC may reduce cancer stemness via sequestering miR-331-3p.

α-Mangostin Inhibits the Activation of Myofibroblasts via Downregulation of Linc-ROR-Mediated TGFB1/Smad Signaling.

Oral submucous fibrosis (OSF) is a premalignant disorder and persistent activation of myofibroblasts is implicated in this pathological progression. Increasing attention has been addressed towards non-coding RNA-regulated myofibroblasts activities and the effects of phytochemicals on non-coding RNA modulation are of great importance. In the present study, we examined the anti-fibrosis property of α-mangostin, a xanthone isolated from the pericarp of mangosteen. We found that α-mangostin exhibited inhibitory potency in myofibroblast activities and expression of fibrosis markers at the concentrations that caused neglectable damage to normal cells. Apart from the downregulation of TGF-ß1/Smad2 signaling, we found that α-mangostin attenuated the expression of long non-coding RNA LincROR as well. Our results demonstrated that the effects of α-mangostin on myofibroblast activation were reverted when LincROR was overexpressed. Additionally, we showed the expression of LincROR in OSF specimens was elevated and silencing of LincROR successfully attenuated myofibroblast characteristics and TGF-ß1/Smad2 activation. Taken together, these findings indicated that the anti-fibrosis effects of α-mangostin merit consideration and may be due to the attenuation of LincROR.

LINC01296 promotes cancer stemness traits in oral carcinomas by sponging miR-143.

Background/purpose: Emerging evidence has shown that various failures in cancer therapy, such as drug resistance, metastasis, and cancer relapse are attributed to cancer stem cells (CSCs). Also, growing attention has been paid to the regulation of non-coding RNAs in cancer stemness. Here, we aimed to investigate the contribution of LINC01296 in the modulation of oral CSCs. Materials and methods: The phenotypic assays including migration, invasion, and colony-forming abilities were carried out in CSCs of two types of oral cancer cells (SAS and GNM) following the knockdown of LINC01296. In addition, the percentage of cells expressing stemness marker, ALDH1, and drug resistance marker, ABCG2, was examined as well as the self-renewal capacity after silencing of LINC01296. Moreover, a luciferase reporter was used to validate the direct interaction between LINC01296 and miR-143. Results: Our results showed that LINC01296 was significantly overexpressed in oral cancer tissues and positively correlated with stemness markers. The phenotypic and flow cytometry assays demonstrated that suppression of LINC01296 reduced the aggressiveness, cancer stemness features, and colony-forming and self-renewal abilities in oral CSCs. Furthermore, we demonstrated that LINC01296 may enhance cancer stemness features through suppression of the effect of miR-143. Conclusion: Silencing of LINC01296 may be a promising direction for oral cancer therapy by reducing cancer stemness via regulation of miR-143.

Expression of carbonic anhydrases I/II and the correlation to clinical aspects of oral squamous cell carcinoma analyzed using tissue microarray.

BACKGROUND: Carbonic anhydrases (CA), a family of metalloenzymes, play an important role in catalyzing the equilibration of carbon dioxide (CO(2)) and carbonic acid (H(2)CO(3)). The role of CAs in tumorigenesis is controversial, especially regarding the expression of CA isoenzymes between various tumor types. This study explores the correlation between the expressions of CA I and CA II and the characteristic features of oral cancer. METHODS: We immunohistochemically examined the expressions of CA I and CA II in 279 cases of oral squamous cell carcinoma (OSCC) using tissue microarrays. Additionally, the oral cancer cell line SCC-9 was used to confirm the relationship between CA I and CA II expression and cell growth. RESULTS: We found a significant correlation between positive CA I and CA II stains and OSCC for more advanced clinical stage (P = 0.014 or 0.012) and larger tumor size (P = 0.008 or 0.038), but not for positive lymph node metastasis, distal metastasis, and recurrence. In vitro analysis also showed that treatment with a CA inhibitor, acetazolamide, inhibited the growth of SCC-9 cells. CONCLUSION: We conclude that expressions of CA I and CA II in OSCC samples can be used to predict local tumor growth in OSCC patients.

Thermally-Induced Deformations and Warpages of Flip-Chip and 2.5D IC Packages Measured by Strain Gauges.

The thermal warpage problems in integrated circuit (IC) packaging exist in both flip-chip and two-and-a-half dimensional integrated circuits (2.5D IC) packages during manufacturing processes and thermal cycling service. This study proposes a simple and easy-to-use strain gauge measurement associated with a beam model theory to determine the thermally induced deformations and warpages of both packages. First, validation and limitations of the beam model theory are presented. Then, the thermally induced out-of-plane deformations for both packages are well described by the finite element method (FEM) simulation with a good consistency to full-field shadow moiré experimental results. The strain gauge measurements were implemented experimentally, and the thermal strain results were found to be well consistent with validated FEM ones. As a result, out-of-plane thermal deformations and warpages of the packages, calculated from the beam model theory with extracted curvature data from the strain gauge, were in reasonably good agreement with those from FEM analysis and shadow moiré measurements. Therefore, the strain gauge method of featuring point strain measurement combined with the beam model theory proved feasible in determining the thermal deformations and warpages of both IC packages.