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Background: Betel quid and its major ingredient, areca nut, are recognized by IARC as major risk factors in oral cancer development. Areca nut extract (ANE) exposure has been linked to OPMD progression and malignant transformation to OSCC. However, the detailed mechanism through which ANE acts on other cell types in the oral microenvironment to promote oral carcinogenesis remains elusive. Methods: Immunoprofiling of macrophages associated with OPMD and OSCC was carried out by immunohistochemical and immunofluorescence staining. Phosphokinase and cytokine arrays and western blotting were performed to determine the underlying mechanisms. Transwell assays were used to evaluate the migration-promoting effect of ANE. Hamster model was finally applied to confirm the in vivo effect of ANE. Results: We reported that M2 macrophages positively correlated with oral cancer progression. ANE induced M2 macrophage differentiation, CREB phosphorylation and VCAM-1 secretion and increased mitochondrial metabolism. Conditioned medium and VCAM-1 from ANE-treated macrophages promoted migration and mesenchymal phenotypes in oral precancer cells. In vivo studies showed that ANE enhanced M2 polarization and related signaling pathways in the oral buccal tissues of hamsters. Conclusion: Our study provides novel mechanisms for areca nut-induced oral carcinogenesis, demonstrating that areca nut promotes M2 macrophage differentiation and secretion of oncogenic cytokines that critically activate malignant transformation of oral premalignant cells. [ABSTRACT FROM AUTHOR]

Background: Punica granatum (pomegranate) potentially ameliorates skin inflammation and pain, including herpetic stromal keratitis. Fermentation is a biotechnological technique that may naturally induce health benefits by producing antioxidants. However, the anti‐aging effect of fermented pomegranate extracts (FPE) on the skin is still unclear. Aim: This investigation evaluates the effects of fermented pomegranate as a functional supplement (FPE drink, FPE‐D) and a cosmetic ingredient (FPE serum, FPE‐S) in vitro and in vivo. Patients/Methods: The effects of FPE products for anti‐oxidation, anti‐tyrosinase, anti‐inflammation, and anti‐aging were examined. Forty subjects were randomly allocated to FPE‐D or placebo drink groups (50 ml of a FPE‐D /placebo drink daily for 8 weeks for each subject), and another 40 subjects were recruited to FPE‐S or placebo serum groups (about 3 ml of a FPE‐S /placebo serum daily and nightly/daily for 4 weeks for each subject) in a double‐blind study. Results: The effects of FPE products on the DPPH, ABTS+, and NO· free radical scavenging activities, their inhibiting of tyrosinase activity and their enhancement of the skin health of healthy subjects, were investigated. FPE‐D improved the moisture, brightness, elasticity, and collagen density of the skin of most subjects at 8 weeks relative to the baseline without treatment (p < 0.05). After 4 weeks of FPE‐S serum consumption, the moisture, brightness, elasticity, spots, UV spots, and collagen density of skin were slightly better than those at week 0 (p < 0.05). Conclusions: The daily consumption of fermented pomegranate extracts can protect the skin against oxidative stress and slow skin aging. [ABSTRACT FROM AUTHOR]

Background: The survival rate of head and neck squamous cell carcinoma (HNSCC) patients with secondary primary malignancy (SPM) showed no significant improvement for decades, however, the impact of advances in diagnostic tools is rarely mentioned. This study investigated the clinical characteristic of HNSCC with SPM over a 27-year period especially from the perspective of diagnostic tools. Methods: This study evaluated 157 HNSCC patients with SPM. The patients were divided into two groups according to the time of SPM diagnosis (Group A:1992–2003; Group B: 2004–2014). Age, gender, stage of first primary malignancy (FPM), SPM interval, overall survival, and disease-free survival were compared between groups. Results: Group B had significantly more SPM developed rate (p = 0.002), more SPM patients with advanced stage of FPM (p = 0.001), synchronous SPM (p = 0.006), and shorter SPM interval (p<0.001) compared to Group A. The survival rate in Group B was not significantly better than Group A. Conclusion: Among patients diagnosed with HNSCC recently, more SPMs are diagnosed in a shorter time interval and in a more advanced stage. The overall advances in diagnostic tools cannot significantly improve SPM survival, however, it enables more patients to receive corresponding treatment. [ABSTRACT FROM AUTHOR]

Objectives: Previously, we demonstrated that IL17RB plays an essential role in lung cancer progression. This study aimed to determine whether IL17RB correlates with oral cancer and promotes oral cancer progression. Subjects and Methods: IL17RB expression in oral cancer tissues and normal tissues was determined by immunohistochemistry staining, while the association of IL17RB expression with the clinicopathological characteristics of oral squamous cell carcinoma (OSCC) patients was analyzed and its correlation with progression‐free survival and response to radiotherapy and chemotherapy in OSCC patients was also explored. Western blotting was performed to investigate the expression of IL17RB in various OSCC cell lines; moreover, transwell assay was performed to evaluate the effect of IL17RB expression on cell migration ability. Results: In this study, we found that IL17RB was expressed higher in OSCC tissues compared to normal oral mucosa tissues and its expression was positively correlated with tumor size, lymph node metastasis, advanced cancer stage, and poor prognosis. In vitro study showed that IL17RB expression in OSCC cell lines as determined by Western blotting, was positively correlated with their migration ability. Conclusion: Clinical and in vitro studies suggest that IL17RB might serve as an independent risk factor and a therapeutic target for oral cancer. [ABSTRACT FROM AUTHOR]

Objectives: To investigate the etiology and ossicular pathology of traumatic ossicular injury in Taiwan and examine the hearing outcomes and predictive factors between the titanium prosthesis and autologous incus groups. Methods: We retrospectively analyzed patients with traumatic ossicular injury from 2011 to 2020 in Taiwan. Patients were divided into the titanium or autologous group according to the surgical materials used. The audiometric outcomes and predictive factors of ossiculoplasty were analyzed between groups. Results: Twenty patients with ossicular chain discontinuity were enrolled (8 in the titanium group and 12 in the autologous group). The postoperative hearing threshold (26.6 ± 8.9 dB) and air-bone gap (10.3 ± 5.6 dB) improved significantly compared with the preoperative hearing threshold (50.7 ± 13.3 dB) and air-bone gap (29.9 ± 11.0 dB). The improvements in the hearing threshold and air-bone gap were not significantly different between the titanium and autologous groups. Our patients presented an improvement in hearing restoration with 65% closure of the air-bone gap in 0 to 10 dB range and 30% in 11 to 20 dB range, without sensorineural hearing loss during surgery. Univariate regression analysis revealed that vertigo, benign paroxysmal positional vertigo, and temporal bone fracture may serve as negative factors influencing the air-bone gap gain. Conclusions: Ossiculoplasty with both titanium prosthesis and autologous materials demonstrated favorable hearing recovery in traumatic ossicular injury. Vertigo, benign paroxysmal positional vertigo, and temporal bone fracture may serve as negative predictive factors of the hearing benefit after surgery. [ABSTRACT FROM AUTHOR]

Squamous cell carcinoma (SCC) is the most common malignant tumor of the head and neck and generally detected in the late stages when the cancer has advanced, and therefore has a poor prognosis and survival rate. A high expression of growth-related oncogene alpha (Groα) is associated with tumor metastasis and invasion and the poor survival rate of patients. Microarray reveals that Groα exhibits a cancer-specific response in HNSCC. Quantitative real-time PCR (qRT-PCR) results concerning the mRNA expression of Groα in HNSCC tissues; indicate that Groα was more highly expressed in HNSCC than in non-cancerous matched tissue (NCMT). The serum of HNSCC patients and healthy subjects demonstrates that the expression of Groα in the HNSCC patients significantly exceeded than in healthy subjects. Furthermore, exposure Groα to stimulated the proliferation, clonogenicity and migration with HNSCC cells (SCC4, SCC9, SCC25 and OECM-1), yielding a stronger response than in non-malignant HaCaT and DOK cells. A high expression of Groα and its receptors CXCR1/2 (chemokine (C-X-C motif) receptor) in HNSCC tissues are highly correlated with tumor progression stage and metastasis. Following the treatment of SCC25 and OECM-1 cells with Groα, β-catenin, matrix metalloproteinases (MMP)-2, MMP-7 and MMP-9 expressions significantly increased but E -cadherin expression was slightly decreased, suggesting that the EMT and metastasis processes were activated by Groα. These findings constitute the first evidence that Groα promotes epithelial mesenchymal transition (EMT) and MMPs expressions in HNSCC via activating CXCR1/2, suggesting a role for Groα in mediating metastasis and its potential as a therapeutic target. [ABSTRACT FROM AUTHOR]

Abstract: Background: Apigenin, a natural plant flavone, may have chemopreventive and therapeutic potentials for anti-inflammatory, antioxidant, and anti-cancer. Nevertheless, the anti-tumor effect of apigenin on human head and neck squamous cell carcinoma (HNSCC) is not fully understood. Methods: The antioxidant capacity and protective effects of apigenin against oxidative stress in murine normal embryonic liver BNLCL2 cells are examined. Cell viability, morphologic change, clonogenic survival, cell cycle distribution, reactive oxygen species (ROS) production, glutathione formation, and death receptors- and Bcl-2-mediated caspase pathways of HNSCC SCC25 cells and A431 cells with apigenin are investigated. Results: Apigenin inhibits the growth of SCC25 and A431 cells and induces cell cycle arrest in the G2/M phase. Apigenin has an antioxidant capacity as well as the ability to inhibit lipid peroxidation. It protects BNLCL2 cells against oxidative damage, and is potentially able to prevent cancer. Apigenin increases intracellular ROS levels and reduces levels of glutathione; it also induces cell apoptosis via tumor necrosis factor receptor (TNF-R)-, TNF-related apoptosis-inducing ligand receptor (TRAIL-R)-, and Bcl-2-mediated caspase-dependent cell death pathways in SCC25 cells. The combination of apigenin with 5-fluorouracil (5-Fu) or cisplatin induces the dramatic death of SCC25 cells. Conclusions: Apigenin induces SCC25 cell apoptosis via the up-regulation of both TNF-R and TRAIL-R signaling pathways, and has a synergistic effect on the inhibition of cell proliferation in combination with 5-Fu or cisplatin. General significance: These analytical findings suggest that apigenin may be a good therapeutic agent against HNSCC cells. [Copyright &y& Elsevier]

This study aimed to investigate whether the progression risk score (PRS) developed from cytoplasmic immunohistochemistry (IHC) biomarkers is available and applicable for assessing risk and prognosis in oral cancer patients. Participants in this retrospective case-control study were diagnosed between 2012 and 2014 and subsequently underwent surgical intervention. The specimens from surgery were stained by IHC for 16 cytoplasmic target markers. We evaluated the results of IHC staining, clinical and pathological features, progression-free survival (PFS), and overall survival (OS) of 102 oral cancer patients using a novel estimation approach with unsupervised hierarchical clustering analysis. Patients were stratified into high-risk (52) and low-risk (50) groups, according to their PRS; a metric consisting of cytoplasmic PLK1, PhosphoMet, SGK2, and SHC1 expression. Moreover, PRS could be extended for use in the Cox proportional hazard regression model to estimate survival outcomes with associated clinical parameters. Our study findings revealed that the high-risk patients had a significantly increased risk in cancer progression compared with low-risk patients (hazard ratio (HR) = 2.20, 95% confidence interval (CI) = 1.10–2.42, p = 0.026). After considering the influences of demographics, risk behaviors, and tumor characteristics, risk estimation with PRS provided distinct PFS groups for patients with oral cancer (p = 0.017, p = 0.019, and p = 0.020). Our findings support that PRS could serve as an ideal biomarker for clinical use in risk stratification and progression assessment in oral cancer. [ABSTRACT FROM AUTHOR]

We synthesized 2-amino-1,3-propanediol-modified boron dipyrromethene (BODIPY) in a rapid two-step synthesis, with a total reaction time of 6 hours. The resulting fluorophore's emission was significantly quenched by polar solvents but increased fourfold upon the addition of Hg2+ ions. Notably, this BODIPY fluorophore exhibited high selectivity toward Hg2+ ions over various other metal ions (Li+, Na+, K+, Ca2+ Co2+, Cu2+, Ni2+, Pb2+, Zn2+, Mn3+, Ag+, and Fe3+), with a binding constant of 7.36 × 104 M−1. The binding mechanism was investigated using proton nuclear magnetic resonance (1H NMR) and infrared (IR) spectroscopy and revealed that 2-amino-1,3-propanediol moieties chelated the Hg2+ ions. These chelated Hg2+ ions could be displaced by hexadentate EDTA molecules. Furthermore, treating BODIPY with an acid restored fluorescence emission, while a base diminished it, and this process was reversible. This rapidly synthesized BODIPY fluorophore holds great potential for Hg2+ ion detection. [ABSTRACT FROM AUTHOR]

Most patients with oral squamous cell cancer (OSCC) have a locally advanced stage at diagnosis. The treatment strategies are diverse, including surgery, radiotherapy and chemotherapy. Despite multimodality treatment, the response rate is unsatisfactory. DNA repair and genetic instability are highly associated with carcinogenesis and treatment outcomes in oral squamous cell cancer, affecting cell growth and proliferation. Therefore, focusing on DNA repair and genetic instability interactions could be a potential target for improving the outcomes of OSCC patients. DNA polymerase-β (POLB) is an important enzyme in base excision repair and contributes to gene instability, leading to tumorigenesis and cancer metastasis. The aim of our study was to confirm POLB regulates the growth of OSCC cells through modulation of cell cycle and chromosomal instability. We analyzed a tissue array from 133 OSCC patients and discovered that low POLB expression was associated with advanced tumor stage and poor overall survival. In multivariate Cox proportional hazards regression analysis, low POLB expression and advanced lymph node status were significantly associated with poor survival. By performing in vitro studies on model cell lines, we demonstrated that POLB silencing regulated cell cycles, exacerbated mitotic abnormalities and enhanced cell proliferation. After POLB depletion, OSCC cells showed chromosomal instability and aneuploidy. Thus, POLB is an important maintainer of karyotypic stability in OSCC cells. [ABSTRACT FROM AUTHOR]

Simple Summary: In head and neck squamous cell carcinoma (HNSCC), more than 60% of patients presenting with locally advanced disease carries a high risk of recurrence and distant metastasis, with a poor prognosis (five-year overall survival (OS), <50%). Therefore, further prevention of recurrence and distant metastasis is crucial for survival improvement in advanced HNSCC patients. In this retrospective study, we investigated the outcomes of metronomic chemotherapy with tegafur–uracil in locally advanced HNSCC (LA HNSCC). Our data showed that adding tegafur–uracil after curative surgery with adjuvant chemoradiotherapy or definitive concurrent chemoradiotherapy significantly improved OS, DFS, and DMFS in patients with LA HNSCC. As a metronomic maintenance regimen, tegafur–uracil was well tolerated with minimal adverse effects. We suggested tegafur–uracil as a maintenance therapy of choice for patients with LA HNSCC. Metronomic chemotherapy inhibits tumor growth by continuous administration of lower-dose chemotherapy. Our study aimed to demonstrate the outcomes of metronomic chemotherapy with tegafur–uracil in locally advanced head and neck squamous cell carcinoma (LA HNSCC). This was a retrospective study including 240 patients with LA HNSCC. After standard treatment, 96 patients were further treated with metronomic tegafur-uracil, and 144 patients were not. No statistical differences were found between both groups with regard to sex, clinical stage, or primary treatment choice. There were more hypopharyngeal cancers and more patients with poor clinicopathological features, including lymphovascular invasion, extranodal extension, and positive margins in the tegafur–uracil group. The median follow-up duration was 31.16 months. Overall survival (OS) was not reached in the tegafur–uracil group and was 54.1 months in the control group (p = 0.008). The median disease-free survival (DFS) was 54.5 months in the tegafur–uracil group and 34.4 months in the control group (p = 0.03). Neither group reached distant metastasis-free survival (DMFS, p = 0.02). In patients with LA HNSCC, adding tegafur–uracil as metronomic chemotherapy after either curative surgery with adjuvant chemoradiotherapy or definitive concurrent chemoradiotherapy significantly improved the OS, DFS, and DMFS with tolerable adverse events. [ABSTRACT FROM AUTHOR]

Background: Streptococcus thermophilus (TCI633) is a probiotic that has been newly isolated from human breast milk, and it can produce hyaluronic acid (HA) when colonizing the gastrointestinal (GI) tract of rodents and humans. A recent study has the established that TCI633 can alleviate synovial tissue inflammation and has potential to mitigate the progression of osteoarthritis. Objective: TCI633 has not been available for use in skincare and this preliminary clinical study will assess its improvement of the skin. Methods: In this study, DNA protection, Hyaluronidase assay, cell viability, and collagen synthesis on human fibroblasts of TCI633 were assessed. Subjects were enrolled in this clinical study and randomly assigned to the TCI633 or placebo group. Each subject was informed to intake two tablets daily for 8 weeks. Each subject was required to undergo skin condition inspection at weeks 0, 4, and 8 and hematology tests to monitor HA, superoxide dismutase (SOD) and catalase levels, and kidney and liver function at weeks 0 and 8. Results: The effects of TCI633 supplementation, including the promotion of skin cell proliferation, the increase of their collagen content, their protection against DNA damage, and the inhibition of hyaluronidase activities, are investigated. Subjects were recruited for an 8‐week long clinical trial to confirm the efficacy of TCI633 in improving the serum biochemical HA, SOD and catalase levels, and anti‐skin age markers. Conclusions: This work provides an alternative approach to improving health, indicating the potential of TCI633 supplementation to delay the aging of skin and improve its condition. [ABSTRACT FROM AUTHOR]

Background: Coffee and coffee products are known potentially to reduce levels of oxidative stress biomarkers in humans. Objective: This investigation evaluates the effects of coffee pulp extract as a functional supplement (in coffee pulp drink, CPD) and a cosmetic ingredient (coffee pulp serum, CPS). Patients/Methods: The effects of CPD and CPS for anti‐oxidation and anti‐aging were investigated. Forty subjects were randomly allocated to CPD or placebo drink groups (50 ml of a CPD/placebo drink daily for 8 weeks for each subject), and another 40 subjects were recruited to CPS or placebo serum groups (about 3 ml of a CPS/placebo serum day and night/daily for 4 weeks for each subject) in a double‐blind study. Results: The CPD and CPS (20%) can increase free radical scavenging activities by 93.3% and 85% (p < 0.001) for DPPH, 94.5% and 61.3% (p < 0.01) for ABTS·+, 43.8% and 15.3% (p < 0.05) for NO· than placebo. The inhibition of tyrosinase activity was increased by 91.6% and 51.0% (p < 0.05) after CPD and CPS application. The CPD comprehensively improved the moisture, brightness, elasticity, spotting, texture, and collagen content of skin for most subjects after 8 weeks, relative to the baseline without treatment (p < 0.05). After 4 weeks of CPS serum consumption, the brightness, elasticity, spotting, UV spots, and collagen content of skin were slightly better than those at week 0 (p < 0.05). Conclusions: The daily consumption of coffee pulp extract products can slow the skin aging process and improve skin health. [ABSTRACT FROM AUTHOR]

Background: Many factors are thought to be associated with the development of cholesteatoma, while the mechanisms of its formation remain unclear. This study aimed to identify the potential mechanisms of the proliferation and growth of cholesteatoma by analysis of the differential expressions of proteins in cholesteatoma and retroauricular skin tissue collected from the same patients. Methods: The present study is a retrospective study performed in an academic medical center. Comparative proteomics analyses using two-dimensional gel electrophoresis (2-DE) and liquid chromatography-tandem mass spectrometry (LC-MS/MS), in addition to immunohistochemical analysis, were conducted to identify differentially-expressed proteins in cholesteatoma tissue as compared with retroauricular skin tissue. Western blotting was also employed to verify the expression patterns of the specific proteins identified by 2-DE and to measure the changes in potential modulators related to cholesteatoma proliferation and growth. Results: Calreticulin (CRT) and annexin A2 (AnxA2) were identified as being differentially-expressed in cholesteatoma by 2-DE and LC-MS/MS, the results of which were in agreement with the results of immunohistochemical analysis and western blotting. Downregulation of CRT and AnxA2 were observed in cholesteatoma. Conclusion: Our data suggests that CRT and AnxA2 downregulation are seen in cholesteatoma compared to retroauricular skin. We speculate that the reduced expression of CRT and the persistent inflammatory response play important roles in the epithelial proliferation of cholesteatoma. [ABSTRACT FROM AUTHOR]

Background: Acne vulgaris is a chronic inflammatory skin disease. If skin lesions are not treated well in time, they can leave a permanent impact on the appearance and a negative influence on personal confidence. The common therapy for acne symptom includes antibiotics, benzoyl peroxide, and azeleic acid. However, those medications have side effects, and the long‐term use should be cautious. Therefore, it is necessary to develop a safe and effective material, which is more suitable for daily use. Objective: Collagen was selected to co‐ferment with three probiotic strains TYCA06/AP‐32/CP‐9 (TAC) due to its excellent feature on wound healing. The fermented material was added into cosmetic gel and applied on subjects' acne lesions. The antimicrobial activity against Propionibacterium acnes and anti‐inflammation effect around lesion area were investigated in a 4‐week clinical study. Material and Methods: An anti‐P. acnes assay, a keratinocytes HaCaT cell‐based wound healing assay, and a cytokine assay on thymic stromal lymphopoietin (TSLP) and interleukin (IL)‐33 were used to evaluate the function of the fermented material in vitro. The TAC/Collagen formula was further incorporated into a cosmetic gel, and the human clinical trial was carried out by applying this gel on 20 volunteers' face with acne vulgaris. The moisture score, sebum content, inflammation, porphyrins numbers, and brown spot number of whole face were observed and recorded. Results: The postbiotics of the TAC/Collagen displayed a good growth inhibition against P. acnes and reduced TSLP and IL‐33 inflammation in vitro. This TAC/Collagen formula enhanced the wound healing in HaCaT cell culture. The result of the clinical trial showed the TAC/Collagen gel improved the moisture score and inflammation index of the skin in vivo. In addition, this TAC/Collagen gel also improved the wound healing of acne symptom in volunteers with acne vulgaris. Moreover, this TAC/Collagen gel reduced the number of the porphyrins and brown spots on facial skin. Conclusion: These postbiotics of TAC/Collagen have beneficial effects on skin health and are able to ameliorate the redness, inflammation, and acne symptom in acne vulgaris patients. [ABSTRACT FROM AUTHOR]

Simple Summary: This is the first study using psychometrics to investigate the association of the DSM-5 betel-quid (BQ)-related symptoms, pathological behaviors, and BQ use disorder (BUD) severity with the risk of oral squamous cell carcinoma (OSCC). This study presents data demonstrating that the symptoms of unsuccessful cutdown of BQ consumption, neglecting major roles, social or interpersonal problems, abandoning or limiting activities, hazardous use, and continued use despite awareness of the dangers were associated with the risk of OSCC. Pathological behavior of risky BQ use enhanced OSCC risk in chewers with moderate-to-severe BUD. BQ chewing is a major risk factor for oral cavity cancers; however, the risk can be mitigated by reducing pathological use. Our study indicates that targeting BUD and establishing a BUD-based strategy is a promising new direction for the prevention of OSCC. The neuroactive alkaloids in betel quid (BQ) can induce BQ addiction. We conducted a case–control study to investigate the effects of BQ-associated DSM-5 symptoms, pathological behaviors, and BQ use disorder (BUD) on oral squamous cell carcinoma (OSCC) risk. A total of 233 patients with newly diagnosed and histopathologically confirmed OSCC and 301 sex- and age-matched controls were included. BQ-related DSM-5 symptoms in the 12 months prior to disease onset were used to measure psychiatric characteristics and BUD. Compared with nonchewers, chewers with the symptoms of unsuccessful cutdown of BQ consumption, neglecting major roles, social or interpersonal problems, abandoning or limiting activities, hazardous use, and continued use despite the awareness of the dangers had a 54.8-, 49.3-, 49.9-, 40.4-, 86.2-, and 42.9-fold higher risk of developing OSCC, respectively. Mild-to-moderate and severe BUD were, respectively, associated with a 8.2–8.5- and 42.3-fold higher OSCC risk, compared with BQ nonuse. Risky BQ use of pathological behavior was associated with a 12.5-fold higher OSCC risk in chewers with no BUD or mild BUD and a 65.0-fold higher risk in chewers with moderate-to-severe BUD (p for risk heterogeneity between the two BUD groups, 0.041). In conclusion, BQ-associated DSM-5 symptoms, pathological behaviors, and BUD severity are associated with the impact of BQ chewing on OSCC development. The pathological behavior of risky BQ use enhances OSCC risk in chewers with moderate-to-severe BUD. Preventing BUD in new BQ users and treating BUD in chewers who already have the disorder are two priorities in areas where BQ chewing is prevalent. [ABSTRACT FROM AUTHOR]

Background: Djulis (Chenopodium formosanum Koidz.) is a cereal food and its antioxidant and pigment constituents may protect skin from photoaging, but conclusive experiments have not been carried out. Objective: This investigation evaluates the effects of djulis extract as a functional supplement. Patients/Methods: In this study, the effects of djulis functional drinks on the free radical scavenging activities, promotion of collagen synthesis and protection against oxidative stress and the effects of ultraviolet B (UVB)‐irradiated of pUC119 DNA were explored. Thirty healthy subjects (aged 35–55 years old) were randomly allocated to djulis or placebo drinks groups (50 ml of a djulis/placebo drink daily for 8 weeks for each subject) in a double‐blind crossover study. Results: The regular consumption of the djulis functional drinks significantly increased levels of the serum biochemical superoxide dismutase (SOD) and catalase (+9.5% and +124.8%) after 8 weeks, relative to baseline controls. The improvements in skin moisture, brightness, elasticity, crow's feet, texture, wrinkles, pores, and collagen content after 8 weeks in the djulis group were +13.3%, +3.8%, +13.2%, −21.8%, −12.1%, −11.0%, −1.4%, and +33.7%, respectively, relative to the baseline without treatment. Conclusions: These work findings suggest the daily consumption of djulis drinks can protect the skin against oxidative stress‐induced damage, delay skin aging and improve skin conditions. [ABSTRACT FROM AUTHOR]

Abstract: Our previous research demonstrated that a novel phenolic glucoside, origanoside, isolated from Origanum vulgare, exhibits significant antimelanogenesis activity. The present study was designed to investigate whether origanoside may serve as a quencher of oxidative insults and is involved in antimelanogenesis. It is found that origanoside exhibit the radical-scavenging capacity of 2,2-diphenyl-1-picrylhydrazyl (DPPH2032;-azinobis(3-ethylbenzothiazoline-6-sulfonic acid) diammonium salt (ABTS +) and superoxide anion radical (O2 −), the reducing power, and the inhibition ability of lipid peroxidation (LP). Pretreatment with origanoside in hydrogen peroxide (H2O2)-treated BNLCL2 and HaCaT cells increased the activities of catalase (CAT) and glutathione peroxidase (GPx), potentially reducing the amount of reactive oxygen species (ROS) generation. These findings confirm the cytoprotective effect of origanoside in hepatocytes and keratinocytes, suggesting that origanoside exhibits antioxidant activities and may be a useful food additive. [Copyright &y& Elsevier]

Background: Sudden sensorineural hearing loss (SSNHL) is a disease with an unknown etiology; damage to the auditory nerve from inflammation due to viral infection or vascular incidents has been implicated. According to several studies, cytokines, including interleukins, are associated with SSNHL in terms of serum expression and genetic polymorphisms. Interleukin-1 (IL-1) plays a key role in inflammation and may be associated with SSNHL. This study analyzed the association of single nucleotide polymorphisms (SNPs) of IL-1 receptor (IL-1R) genes with SSNHL in Taiwan. Methods: We conducted a case–control study involving 401 patients with SSNHL and 730 healthy controls. Four SNPs (IL-1R type 1 gene [IL1R1] [rs3917225 and rs2234650] and IL-1R type 2 gene [IL1R2] [rs4141134 and rs2071008]) were selected. The genotypes were determined using the TaqMan assay. The Hardy–Weinberg equilibrium (HWE) was tested for each SNP, and genetic effects were evaluated. Results: The TT genotype of rs2234650 had an adjusted odds ratio (OR) of 2.988 (95% confidence interval [95% CI] 1.27–6.82) (P = 0.012) compared with the CC genotype in patients with SSNHL. The SNP rs2234650 was associated with SSNHL in the recessive model (TT vs. CC + CT, P = 0.0206, OR = 2.681). The CT genotype of rs4141134 had an adjusted OR of 3.860 (95% CI 2.01–7.44; P < 0.0001) compared with the TT genotype, in patients with SSNHL. The SNP rs4141134 was associated with SSNHL under the dominant model (CC + CT vs. TT, P < 0.0001, OR = 4.087). Conclusion: These findings suggest that IL1R1 and IL1R2 gene polymorphisms may contribute to an increased risk of SSNHL in Taiwan. [ABSTRACT FROM AUTHOR]

Background: Sudden sensorineural hearing loss (SSNHL) is a disease with an unknown etiology; damage to the auditory nerve from inflammation due to viral infection or vascular incidents has been implicated. According to several studies, cytokines, including interleukins, are associated with SSNHL in terms of serum expression and genetic polymorphisms. Interleukin-1 (IL-1) plays a key role in inflammation and may be associated with SSNHL. This study analyzed the association of single nucleotide polymorphisms (SNPs) of IL-1 receptor (IL-1R) genes with SSNHL in Taiwan. Methods: We conducted a case–control study involving 401 patients with SSNHL and 730 healthy controls. Four SNPs (IL-1R type 1 gene [IL1R1] [rs3917225 and rs2234650] and IL-1R type 2 gene [IL1R2] [rs4141134 and rs2071008]) were selected. The genotypes were determined using the TaqMan assay. The Hardy–Weinberg equilibrium (HWE) was tested for each SNP, and genetic effects were evaluated. Results: The TT genotype of rs2234650 had an adjusted odds ratio (OR) of 2.988 (95% confidence interval [95% CI] 1.27–6.82) (P = 0.012) compared with the CC genotype in patients with SSNHL. The SNP rs2234650 was associated with SSNHL in the recessive model (TT vs. CC + CT, P = 0.0206, OR = 2.681). The CT genotype of rs4141134 had an adjusted OR of 3.860 (95% CI 2.01–7.44; P < 0.0001) compared with the TT genotype, in patients with SSNHL. The SNP rs4141134 was associated with SSNHL under the dominant model (CC + CT vs. TT, P < 0.0001, OR = 4.087). Conclusion: These findings suggest that IL1R1 and IL1R2 gene polymorphisms may contribute to an increased risk of SSNHL in Taiwan. [ABSTRACT FROM AUTHOR]

The engineering of biomaterials provides an opportunity for developing new polymeric composites. In this context, the objective of this work is to produce and evaluate fiber obtained from mixtures of corn straw waste and polylactic acid (PLA) in vitro. Treated corn straw fiber (TCSF) was made by cutting corn straw waste and applying alkali, acid, and silane treatments. Corn straw fiber (CSF) or TCSF was combined with PLA or modified PLA (MPLA) in an electrospinning technique, to manufacture a 100–500 nm nanofiber mat. We studied morphology, mechanical properties, water resistance, biodegradability, and cytocompatibility properties of the electrospun PLA/CSF and MPLA/TCSF nanofibers. The resulting tensile properties and morphological characterizations indicated enhanced adhesion between TCSF and MPLA in the nanofiber, as well as improved water resistance and tensile strength, compared to PLA/CSF nanofiber. Regarding biocompatibility, only viable cells were found for all of the compositions, and the biocompatibility of the materials was validated by morphological analysis of cultured cells. Morphology proliferation assays showed that human keratinocyte cells grow well on the surfaces of PLA, MPLA, and their composite nanofibers. The weight loss of PLA/CSF and MPLA/TCSF composites buried in soil indicated that both were biodegradable, especially at high levels of CSF or TCSF substitution. [ABSTRACT FROM AUTHOR]

Background: The efficacy of Djulis for skin care is currently based on cellular or animal models, and the clinical aspect is not in place. Aim: This clinical study is to investigate the synergistic effect of fish collagen and Djulis (Chenopodium formosanum Koidz.) for improvement of skin parameters. We used the combination of hydrolyzed collagen and Djulis to develop a new functional formula for skin improvement. Patients/Methods: Fifty volunteers were randomly allocated (in a 1:1 ratio) to the placebo or collagen drink group. Volunteers were required to consume a 50 mL of a collagen drink or placebo drink daily for 8 weeks. For measurements, the indexes of skin conditions were measured at the baseline and 4 and 8 weeks. Results: The improvements of skin hydration, brightness, crow's feet, texture, wrinkles, pores, spots, and collagen content after 8 weeks in collagen group were 17.8%, 5.4%, 14.9%, 9.9%, 29.3%, 10.4%, 9.9%, and 22.3%, respectively. Noticeably, over 68% of subjects got improved for their skin parameters after 8‐week intake of collagen drink. The improvement levels indicated competitive skin improvement effects in comparison with previous studies. Conclusion: This clinical study demonstrates the synergistic effect of fish collagen and Djulis (the main components) for the substantial improvements in hydration, brightness, crow's feet, texture, wrinkles, pores, surface spots, and collagen content in skin. The collagen drink comprehensively improved skin parameters for most subjects after 4‐week intake and manifested competitive efficiency in comparison with other similar studies. We convince that the collagen drink may delay skin aging process and improve skin aging parameters. [ABSTRACT FROM AUTHOR]

Recurrent locally advanced or metastatic head and neck squamous cell carcinoma (HNSCC) is associated with dismal prognosis because of its highly invasive behavior and resistance to conventional intensive chemotherapy. The combination of targeted therapy and conventional chemotherapy has significantly improved clinical outcomes. In recent years, the development of immunotherapies, such as immune checkpoint inhibitors (ICIs), has further increased treatment responses and prolonged survival. However, the limited response rate, risk of immunotherapy-related adverse effects and high cost of immunotherapy make the identification of predictive markers to optimize treatment efficacy a critical issue. Biomarkers are biological molecules that have been widely utilized to predict treatment response to certain treatments and clinical outcomes or to detect disease. An ideal biomarker should exhibit good predictive ability, which can guide healthcare professionals to achieve optimal treatment goals and bring clinical benefit to patients. In this review, we summarized the results of recent and important studies focused on HNSCC ICI immunotherapy and discussed potential biomarkers including their strengths and limitations, aiming to gain more insight into HNSCC immunotherapy in real world clinical practice. [ABSTRACT FROM AUTHOR]

Objectives: VELscope® was developed to inspect oral mucosa autofluorescence. However, its accuracy is heavily dependent on the examining physician's experience. This study was aimed toward the development of a novel quantitative analysis of autofluorescence images for oral cancer screening.Materials and Methods: Patients with either oral cancer or precancerous lesions and a control group with normal oral mucosa were enrolled in this study. White light images and VELscope® autofluorescence images of the lesions were taken with a digital camera. The lesion in the image was chosen as the region of interest (ROI). The average intensity and heterogeneity of the ROI were calculated. A quadratic discriminant analysis (QDA) was utilized to compute boundaries based on sensitivity and specificity.Results: 47 oral cancer lesions, 54 precancerous lesions, and 39 normal oral mucosae controls were analyzed. A boundary of specificity of 0.923 and a sensitivity of 0.979 between the oral cancer lesions and normal oral mucosae were validated. The oral cancer and precancerous lesions could also be differentiated from normal oral mucosae with a specificity of 0.923 and a sensitivity of 0.970.Conclusion: The novel quantitative analysis of the intensity and heterogeneity of VELscope® autofluorescence images used in this study in combination with a QDA classifier can be used to differentiate oral cancer and precancerous lesions from normal oral mucosae. [ABSTRACT FROM AUTHOR]

Abstract: Background: Skin cancers are reportedly increasing worldwide. Developing novel anti-skin cancer drugs with minimal side effects is necessary to address this public health issue. Sinuleptolide has been demonstrated to possess anti-cancer cell activities; however, the mechanisms underlying the anti-skin cancer effects of 5-epi-sinuleptolide and sinuleptolide remain poorly understood. Methods: Apoptosis cell, cell-cycle-related regulatory factors, and mitochondria- and death receptor-dependent caspase pathway in 5-epi-sinuleptolide-induced cell apoptosis were examined using SCC25 cells. Results: 5-epi-Sinuleptolide inhibited human skin cancer cell growth more than did sinuleptolide. Treatment of SCC25 cells with 5-epi-sinuleptolide increased apoptotic body formation, and induced cell-cycle arrest during the G2/M phase. Notably, 5-epi-sinuleptolide up-regulated p53 and p21 expression and inhibited G2/M phase regulators of cyclin B1 and cyclin-dependent kinease 1 (CDK1) in SCC25 cells. Additionally, 5-epi-sinuleptolide induced apoptosis by mitochondria-mediated cytochrome c and Bax up-expression, down-regulated Bcl-2, and activated caspase-9 and -3. 5-epi-Sinuleptolide also up-regulated tBid, which is associated with up-regulation of tumor necrosis factor-α (TNF-α) and Fas ligand (FasL) and their cognate receptors (i.e., TNF-RI, TNF-R2 and Fas), downstream adaptor TNF-R1-associated death domain (TRADD) and Fas-associated death domain (FADD), and activated caspase-8 in SCC25 cells. Conclusions: The analytical results indicate that the death receptor- and mitochondria-mediated caspase pathway is critical in 5-epi-sinuleptolide-induced apoptosis of skin cancer cells. General significance: This is the first report suggesting that the apoptosis mediates the anti-tumor effect of 5-epi-sinuleptolide. The results of this study might provide useful suggestions for designing of anti-tumor drugs for skin cancer patients. [Copyright &y& Elsevier]

Simple Summary: The prevention and treatment of cancers of the oral cavity and pharynx are currently important issues for national health. Currently, the incidence of oral cavity and pharynx cancers is globally the highest in Taiwanese men. Regarding the occurrence of oral cavity and pharynx cancers and oral potentially malignant disorders (OPMD), no report has ascertained how betel quid (BQ) can induce the expression of monoamine oxidase (MAO) and catechol-O-methyltransferase (COMT). We aimed to explore the role and clinical significance of specific markers of BQ exposure and human susceptibility to MAO and COMT. Our findings highlight the association of MAO and COMT biomarkers to risks of oral and pharyngeal cancers and OPMD. These novel findings will provide important strategies for disease prevention, early clinical diagnosis, and treatment effectiveness, and will offer a strong foundation to reduce BQ-related cancers of the oral cavity and pharynx and OPMD. Betel quid (BQ), a group I human carcinogen, strongly contributes to an increased risk of oral potentially malignant disorders (OPMD) and cancers of the oral cavity and pharynx. This study was conducted to discover whether monoamine oxidase (MAO) and catechol-O-methyltransferase (COMT) variants play a potential role in the risk assessment of oral cavity and pharynx cancers and OPMD, particularly among BQ users. We applied a case–control study to confirm the polymorphism of MAO and COMT using single-nucleotide polymorphisms. We used qRT-PCR, Western blotting, and immunohistochemistry (IHC) to determine MAO and COMT expression. Carriers of the MAOA rs6323 G-allele, MAOB rs6324 G-allele, and COMT rs4633 C/C-genotype had a prominently increased risk of oral cavity and pharynx cancers (AOR = 56.99; p < 0.001). Compared to adjacent noncancerous tissues, a significant downregulation of MAO and COMT expression was exhibited in cancerous tissues (p < 0.01). Furthermore, in different cell models, MAO and COMT expression was significantly downregulated with an increased dose of arecoline (p < 0.01). In personalized preventive medicine for oral and pharyngeal cancers, our findings are the first to demonstrate the potential role of lower MAO and COMT expression levels, with the risk polymorphisms utilized as clinical biomarkers. [ABSTRACT FROM AUTHOR]

The aim of this single-center case-control study is to investigate the feasibility and accuracy of oral cancer protein risk stratification (OCPRS) to analyze the risk of cancer progression. All patients diagnosed with oral cancer in Taiwan, between 2012 and 2014, and who underwent surgical intervention were selected for the study. The tissue was further processed for immunohistochemistry (IHC) for 21 target proteins. Analyses were performed using the results of IHC staining, clinicopathological characteristics, and survival outcomes. Novel stratifications with a hierarchical clustering approach and combinations were applied using the Cox proportional hazard regression model. Of the 163 participants recruited, 102 patients were analyzed, and OCPRS successfully identified patients with different progression-free survival (PFS) profiles in high-risk (53 subjects) versus low-risk (49 subjects) groups (p = 0.012). OCPRS was composed of cytoplasmic PLK1, phosphoMet, and SGK2 IHC staining. After controlling for the influence of clinicopathological features, high-risk patients were 2.33 times more likely to experience cancer progression than low-risk patients (p = 0.020). In the multivariate model, patients with extranodal extension (HR = 2.66, p = 0.045) demonstrated a significantly increased risk for disease progression. Risk stratification with OCPRS provided distinct PFS groups for patients with oral cancer after surgical intervention. OCPRS appears suitable for routine clinical use for progression and prognosis estimation. [ABSTRACT FROM AUTHOR]

Simple Summary: Esophageal squamous cell neoplasms (ESCNs) are the most common second primary neoplasm in patients with head and neck squamous cell carcinoma (HNSCC). In this 10-year endoscopic surveillance cohort, we prospectively screened and followed up incident HNSCC patients to develop metachronous ESCN. We found initial Lugol voiding lesion classification could be a predictor for development of metachronous ESCN. Narrow band image helps in identifying existing ESCN but lack of scores on the mucosal background to predict the risk of metachronous ESCN. Therefore, we recommend image enhanced endoscopy including Lugol chromoendoscopy as the screening tool for incident HNSCC patients. Esophageal squamous cell neoplasms (ESCNs) are the most common second primary neoplasm in patients with head and neck squamous cell carcinoma (HNSCC), and few studies have focused on metachronous ESCNs. We aimed to evaluate the incidence of and risk factors for metachronous ESCNs and to provide a reasonable endoscopic follow-up plan for HNSCC patients. We extended our prospective cohort since October 2008 by recruiting incident HNSCC patients. All enrolled patients were interviewed to collect information on substance use (smoking, alcohol, and betel nut) and esophagogastroduodenoscopy (EGD) with Lugol chromoendoscopy results for synchronous ESCNs soon after HNSCC diagnosis. Endoscopic screenings for metachronous ESCNs were performed 6 to 12 months after the previous examinations. A total of 1042 incident HNSCC patients were enrolled, but only 175 patients met all the criteria and were analyzed. A total of 20 patients had metachronous ESCNs (20/175, 11.4%). Only the initial Lugol-voiding lesion (LVL) classification significantly predicted the development of metachronous ESCNs. Patients with an LVL classification of C/D had a higher risk of developing metachronous ESCNs than those with an LVL classification of A/B (adjusted odds ratio: 5.03, 95% confidence interval: 1.52–16.67). The mean interval for developing metachronous ESCNs was 33 months, but the shortest interval for developing metachronous esophageal squamous cell carcinoma was 12 months. Lugol chromoendoscopy screening among incident HNSCC patients predicts the risk of developing metachronous ESCNs. A closer follow-up with an endoscopy every 6 months is recommended for those with LVL classifications of C and D. [ABSTRACT FROM AUTHOR]

Betel quid (BQ) has been classified as a Group I human carcinogen in light of evidence demonstrating an association with an elevated risk of oral and pharyngeal cancers. To date, the incidence rate of oral and pharynx cancers among Taiwanese men ranks the highest worldwide. However, no study has yet confirmed variants of CYP26A1 was associated with the risks of oral and pharyngeal cancers. A case-control study was conducted (n = 339). CYP26A1 polymorphism was performed using SNP assay. Real-time qRT-PCR and Western blotting were used to determine the levels of CYP26A1 expression. The cancer cell model involved treatment with arecoline. Our findings showed that the downregulation of CYP26A1 mRNA and protein expression are more frequently observed in cancerous tissues than adjacent normal tissues in patients with oral and pharynx cancers (p < 0.01). We found that CYP26A1 was downregulated as the arecoline dose increased. We hypothesized that lower levels of CYP26A1 mRNA expression can be utilized a clinically biomarker causes oral and pharynx cancers. Arecoline appears to modulate CYP26A1 expression through specific pathways. Carriers of CYP26A1 SNP, rs2068888 (G/G)/rs4418728 (G/G) and who have lower levels of CYP26A1 expression are associated with an increased risk of oral and pharyngeal cancers. [ABSTRACT FROM AUTHOR]

Objectives: In current guidelines, early tongue cancer status post partial glossectomy without adverse risk features do not require adjuvant treatment. However, many of these patients developed recurrence with neck metastases soon. The objectives of this study were to investigate the potential risk factors in early tongue cancer that prophylactic management of neck may be considered.Materials and Methods: From January 2010 to September 2015, this retrospective study enrolled 102 patients with T1-2N0 primary oral tongue squamous cell carcinoma according to AJCC 8th edition Cancer Staging System. All patients underwent partial glossectomy with or without selective neck dissection, and did not receive any adjuvant treatment. Patients with any adverse risk features were excluded. We have studied the 4-year cancer-specific survival and neck recurrence rate, and analyzed the relevance between pathologic tumor classification, tumor depth, tumor histologic grade, and measured surgical margin of primary tumor.Results: The median follow up duration was 47 months (range 6-93 months) with the median recurrence interval was 13 months. Histologic grade ≥2 of primary tumor was significantly associated with increased risk of neck recurrence and disease-specific mortality in both univariate and multivariate analysis.Conclusion: Histologic grade ≥2 was an adverse prognostic factor of neck recurrence and was significantly associated with poor cancer-specific survival in T1-2N0 early oral tongue cancer patients. Therefore, prophylactic neck dissection or prophylactic adjuvant radiation therapy to neck may be considered in T1-2N0 early oral tongue cancer with histologic grade ≥2 of primary tumor. [ABSTRACT FROM AUTHOR]