Search

Anti-aging biomaterial (CSDB) ameliorates tissue and cell potential dysfunction through reprogramming stem cells from a senescence state and altering the extracellular matrix microenvironment (ECM) to prolong longetivity.

The present study was to investigate the rheological property, printability, and cell viability of alginate–gelatin composed hydrogels as a potential cell-laden bioink for three-dimensional (3D) bioprinting applications. The 2 g of sodium alginate dissolved in 50 mL of phosphate buffered saline solution was mixed with different concentrations (1% (0.5 g), 2% (1 g), 3% (1.5 g), and 4% (2 g)) of gelatin, denoted as GBH-1, GBH-2, GBH-3, and GBH-4, respectively. The properties of the investigated hydrogels were characterized by contact angle goniometer, rheometer, and bioprinter. In addition, the hydrogel with a proper concentration was adopted as a cell-laden bioink to conduct cell viability testing (before and after bioprinting) using Live/Dead assay and immunofluorescence staining with a human corneal fibroblast cell line. The analytical results indicated that the GBH-2 hydrogel exhibited the lowest loss rate of contact angle (28%) and similar rheological performance as compared with other investigated hydrogels and the control group. Printability results also showed that the average wire diameter of the GBH-2 bioink (0.84 ± 0.02 mm (*** p < 0.001)) post-printing was similar to that of the control group (0.79 ± 0.05 mm). Moreover, a cell scaffold could be fabricated from the GBH-2 bioink and retained its shape integrity for 24 h post-printing. For bioprinting evaluation, it demonstrated that the GBH-2 bioink possessed well viability (>70%) of the human corneal fibroblast cell after seven days of printing under an ideal printing parameter combination (0.4 mm of inner diameter needle, 0.8 bar of printing pressure, and 25 °C of printing temperature). Therefore, the present study suggests that the GBH-2 hydrogel could be developed as a potential cell-laden bioink to print a cell scaffold with biocompatibility and structural integrity for soft tissues such as skin, cornea, nerve, and blood vessel regeneration applications.

Oral squamous cell carcinoma (OSCC) is a type of malignancy characterized by high relapse and recurrence rates in the late stage despite optimal surgical intervention and postoperative chemoradiotherapy. Because the management of relapse following definitive treatment is challenging, accurate risk stratification is of clinical significance to improve treatment outcomes. Circular RNAs (circRNAs) are noncoding RNAs featured with cell-type specificity and high stability, owing to their circular structure, making these molecules excellent biomarkers for a variety of diseases.The levels of hsa_circ_0000190 and 0001649 in plasma samples from 30 healthy controls and 66 OSCC patients were determined by droplet digital polymerase chain reaction. The same primer sets were used with PCR to examine the expression of these two circRNAs in cancerous and adjacent normal tissues. A receiver operating characteristics curve was generated to evaluate the diagnostic value. The Kaplan-Meier method with a log-rank test was used for survival analysis.We identified two circRNAs as potential biomarkers for OSCC, showing that the plasma level of hsa_circ_0000190 was significantly decreased in the late stage and marginally correlated with the development of second primary OSCC. We also found that the decreased plasma hsa_circ_0001649 was correlated with the recurrence and poor prognosis of patients. Additionally, we found that high plasma hsa_circ_0000190, but not hsa_circ_0001649, possibly predicted a better response of patients to induction chemotherapy.Our study demonstrated the potential of biomarkers in plasma to inform not just the tumor but the entire oral cavity, thereby offering a prediction for early recurrence and second primary OSCC. The plasma circRNAs remain valuable for OSCC, albeit the easy accessibility to the oral cavity.

Apart from aging process, adult intervertebral disc (IVD) undergoes various degenerative processes. However, the nicotine has not been well identified as a contributing etiology. According to a few studies, nicotine ingestion through smoking, air or clothing may significantly accumulate in active as well as passive smokers. Since nicotine has been demonstrated to adversely impact various physiological processes, such as sympathetic nervous system, leading to impaired vasculature and cellular apoptosis, we aimed to investigate whether nicotine could induce IVD degeneration. In particular, we evaluated dose-dependent impact of nicotine in vitro to simulate its chronic accumulation, which was later treated by platelet-derived biomaterials (PDB). Further, during in vivo studies, mice were subcutaneously administered with nicotine to examine IVD-associated pathologic changes. The results revealed that nicotine could significantly reduce chondrocytes and chondrogenic indicators (Sox, Col II and aggrecan). Mice with nicotine treatment also exhibited malformed IVD structure with decreased Col II as well as proteoglycans, which was significantly increased after PDB administration for 4 weeks. Mechanistically, PDB significantly restored the levels of IGF-1 signaling proteins, particularly pIGF-1 R, pAKT, and IRS-1, modulating ECM synthesis by chondrocytes. Conclusively, the PDB impart reparative and tissue regenerative processes by inhibiting nicotine-initiated IVD degeneration, through regulating IGF-1/AKT/IRS-1 signaling axis.

The present study established a maximum standard for printing quality and developed a preliminary ideal index to print three-dimensional (3D) construct using the Gly-Arg-Gly-Asp (GRGD) peptide modified Pluronic-F127 hydrogel (hereafter defined as 3DG bioformer (3BE)) as bioink. In addition, the biocompatibility of 3BE for 3D printing applications was carefully investigated. For biocompatibility study and ideal printing parameter, we used the formulation of 3BE in three different concentrations (3BE-1: 25%, 3BE-2: 30%, and 3BE-3: 35%). The 3BE hydrogels were printed layer by layer as a cube-like construct with all diameters of the needle head under the same feed (100 mm/s). The printing parameters were determined using combinations of 3BE-1, 3BE-2, and 3BE-3 with three different standard needle sizes (&Phi, 0.13 mm, &Phi, 0.33 mm, and &Phi, 0.9 mm). The printed constructs were photographed and observed using optical microscopy. The cell viability and proliferation were evaluated using Live/Dead assay and immunofluorescence staining. Results showed that a stable of printed line and construct could be generated from the 3BE-3 combinations. Cytotoxicity assay indicated that the 3BE hydrogels possessed well biocompatibility. Bioprinting results also demonstrated that significant cell proliferation in the 3BE-3 combinations was found within three days of printing. Therefore, the study discovered the potential printing parameters of 3BE as bioink to print a stable construct that may also have high biocompatibility for cell encapsulation. This finding could serve as valuable information in creating a functional scaffold for tissue engineering applications.

Background Recurrent aphthous stomatitis (RAS) is considered a prophase symptom in patients with specific cancers. This study assessed the association between RAS and subsequent onset of cancer based on a nationwide population‐based database in Taiwan. Materials and Methods We selected study participants from the National Health Insurance Research Database from January 2000 to December 2008. Patients in the non‐RAS cohort were matched to case study patients at a 1:1 ratio through frequency matching. All participants were followed up for at least 5 years, and those who received cancer diagnoses during follow‐up were identified. Results Among 52 307 patients with and 52 304 patients without RAS, the combined hazard ratio (HR) of all subsequent cancer cases was 1.3 (95% confidence interval [CI]: 1.25‐1.35, P = 0). RAS diagnosis was associated with risk for cancers of the head and neck (aHR = 2, 95% CI: 1.8‐2.3), colon (aHR = 1.2, 95% CI: 1.1‐1.4), liver (aHR = 1.1, 95% CI: 1‐1.3), pancreas (aHR = 1.4, 95% CI: 1.1‐1.7), skin (aHR = 1.4, 95% CI: 1.2‐1.7), breast (aHR = 1.2, 95% CI: 1.1‐1.4), and prostate (aHR = 1.5, 95% CI: 1.3‐1.8), as well as hematologic cancers (aHR = 1.6, 95% CI: 1.3‐1.9). A higher risk was observed for male patients (aHR = 1.35, 95% CI: 1.28‐1.42) than for female patients (aHR = 1.25, 95% CI: 1.18‐1.31) with RAS. Conclusions RAS was associated with specific cancers. Susceptible RAS patients should be screened for specific cancers.

High morbidity and mortality of diabetes mellitus (DM) throughout the human population is a serious threat which needs to be addressed cautiously. Type 1 diabetes mellitus (T1DM) and type 2 diabetes mellitus (T2DM) are most prevalent forms. Disruption in insulin regulation and resistance leads to increased formation and accumulation of advanced end products (AGEs), which further enhance oxidative and nitrosative stress leading to microvascular (retinopathy, neuropathy, and nephropathy) and macrovascular complications. These complications affect the normal function of organ and tissues and may cause life-threatening disorders, if hyperglycemia persists and improperly controlled. Current and traditional treatment procedures are only focused on to regulate the insulin level and do not cure the diabetic complications. Pancreatic transplantation seemed a viable alternative; however, it is limited due to lack of donors. Cell-based therapy such as stem cells is considered as a promising therapeutic agent against DM and diabetic complications owing to their multilineage differentiation and regeneration potential. Previous studies have demonstrated the various impacts of both pluripotent and multipotent stem cells on DM and its micro- and macrovascular complications. Therefore, this review summarizes the potential of stem cells to treat DM and its related complications.

In this study, the wound healing properties of the gelatin-based hydrogel (GBH) wound dressing combined with adipose-derived stem cells (ADSCs) were investigated using the mouse and porcine models. The analytical results showed that the ADSCs harvested from the porcine significantly increased cell growth and promoted cell differentiation (adipogenesis and osteogenesis) in comparison to the ADSCs harvested from the mouse in vitro. Moreover, the in vivo results also indicated that the GBH wound dressing combined with ADSCs and its culture medium could potentially accelerate wound healing in the mouse and porcine models. The ADSCs presented a possibility of recovery from wounds and injuries through skin regeneration. Therefore, both in vitro and in vivo results demonstrated that the ADSCs can potentially be an effective clinical treatment through the GBH wound dressing, which is a promising evidence-based complementary and alternative medicine for skin regeneration. © 2018 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 107B: 278-285, 2019.

Background/purpose: Whether third molars contribute to or aggravate relapse, particularly in the mandibular dental arch, after orthodontic treatment remains controversial. Orthodontic clinicians vary widely in their practice regarding prophylactic third molar removal after orthodontic treatment. The present study systematically reviewed and meta-analyzed the available literature, and assessed the impact of third molar removal on the relapse of mandibular dental arch alignment after orthodontic treatment. Materials and methods: Relevant literature was searched on online databases, namely Pubmed, Embase, and Cochrane. Outcomes of post-orthodontic mandibular relapse were evaluated in terms of the Little's irregularity index, intermolar width, and arch length. Statistical analysis was conducted using the Review Manager software (Version 5.3, The Cochrane Collaboration, Oxford, England). Results: Our initial search strategy yielded 360 citations, of which three retrospective studies were selected. The Little's irregularity index (weighted mean difference = 0.80, 95% confidence interval = 0.13–1.47, P = 0.02) differed significantly between the erupted third molar extraction group and agenesis third molar group; whereas the arch length and intermolar width did not. No outcome differed significantly between the impacted third molar extraction group and agenesis third molar group. Conclusion: Removal of the mandibular third molars is recommended for alleviating or preventing long-term incisor irregularity. Keywords: little's irregularity index, post-orthodontic mandibular relapse, prophylactic third molar removal, third molars

In current study, we have investigated the anti-oral cancer effects of developed functional beverage, which integrates fucoidan complex (FC) with natural/organic ingredients including vegetable juice (V), mulberry (M) and wheatgrass (W), designated as VMW-FC cocktail. FC has been recognized as functional food with nutraceutical characteristics, other cocktail components are known to individually contain luxuriant bioactive factors including sulfated polysaccharides and polyphenols etc., exerting various curative impacts. Our results demonstrated that VMW-FC significantly inhibited oral cancer proliferation in a dose- and time-dependent manner. It also retarded cell cycle regulators (CDKs and cyclins) and upregulated cyclin-dependent kinase inhibitor p21. Additionally, VMW-FC suppressed cell migration along with inhibited EMT markers. Further, VMW-FC significantly attenuated xenograft tumor growth in NOD-SCID mice without further adverse effects. Conclusively, VMW-FC strongly inhibits oral cancer through inducing apoptosis, G2/M cell cycle arrest and reducing migration-related EMT markers, which may be primarily attributed to sulfated polysaccharides in beverage cocktail.

// Ming-Yi Lu 1, 2, * , Yi-Wen Liao 1, * , Pei-Yin Chen 1, 2 , Pei-Ling Hsieh 3 , Chih-Yuan Fang 4, 5 , Chia-Yu Wu 5, 6 , Ming-Liang Yen 6 , Bou-Yue Peng 5, 6 , Dayen Peter Wang 5, 6 , Hsin-Chung Cheng 5, 6 , Ching-Zong Wu 5, 6 , Yung-Hsun Shih 4, 6 , Duen-Jeng Wang 6 , Cheng-Chia Yu 1, 2, 3 and Lo-Lin Tsai 4, 6 1 School of Dentistry, Chung Shan Medical University, Taichung, Taiwan 2 Department of Dentistry, Chung Shan Medical University Hospital, Taichung, Taiwan 3 Institute of Oral Sciences, Chung Shan Medical University, Taichung, Taiwan 4 Department of Dentistry, Taipei Municipal Wanfang Hospital, Taipei, Taiwan 5 School of Dentistry, College of Oral Medicine, Taipei Medical University, Taipei, Taiwan 6 Department of Dentistry, Taipei Medical University Hospital, Taipei, Taiwan * These authors have contributed equally to this work Correspondence to: Cheng-Chia Yu, email: ccyu@csmu.edu.tw Lo-Lin Tsai, email: lolintsai@tmu.edu.tw Keywords: oral squamous cell carcinomas; long non-coding RNA; HOTAIR; cancer stem cells; mesenchymal Received: May 16, 2017 Accepted: August 26, 2017 Published: October 07, 2017 ABSTRACT Increasing evidence indicates that long non-coding RNAs (lncRNAs) regulate diverse cellular processes, such as cell growth, apoptosis and tumorigenesis. However, the functional roles of lncRNAs and mechanistic analysis of their interplays with oncogenic pathways in oral cancer remain largely unknown. In the current study, we examined the significance of lncRNA HOTAIR (HOX transcript antisense RNA) in tumor progression of oral squamous cell carcinomas (OSCC). We found the expression of HOTAIR was upregulated in tumor tissues, especially in the metastatic samples. And it was also observed in metastatic OSCC cell lines. Silence of HOTAIR in oral carcinomas stem cells (OCSC) significantly inhibited their cancer stemness, invasiveness and tumourigenicity in xenotransplantation models. By contrast, overexpression of HOTAIR in OSCC enhanced their metastatic potential and epithelial-mesenchymal transition (EMT) characteristics. And we showed that the expression of HOTAIR was positively related to mesenchymal markers and inversely correlated with epithelial marker in clinical samples. Moreover, Kaplan-Meier survival analysis suggested that high level of HOTAIR was a strong predictor of poor survival in OSCC patients. Collectively, our data demonstrated that HOTAIR-mediated cancer stemness and metastasis are associated with the regulation of EMT and HOTAIR may serve as a therapeutic target in OSCC.

// Bou-Yue Peng 1 , Chi-Sheng Chiou 2, 3 , Navneet Kumar Dubey 4, 5 , Sung-Hsun Yu 4, 6 , Yue-Hua Deng 4, 7 , Feng-Chou Tsai 8 , Han-Sun Chiang 7 , Ying-Hua Shieh 10, 11 , Wei-Hong Chen 4 and Win-Ping Deng 2, 4, 9 1 Oral and Maxillofacial Surgery Section, Department of Dentistry, Taipei Medical University Hospital, Taipei, Taiwan 2 School of Dentistry, College of Oral Medicine, Taipei Medical University, Taipei, Taiwan 3 Division of Allergy, Immunology and Rheumatology, Department of Internal Medicine, Taipei Medical University Hospital, Taipei, Taiwan 4 Stem Cell Research Center, College of Oral Medicine, Taipei Medical University, Taipei, Taiwan 5 Graduate Institute of Biomedical Materials and Tissue Engineering, College of Biomedical Engineering, Taipei Medical University, Taipei, Taiwan 6 Graduate Institute of Medical Sciences, College of Medicine, Taipei Medical University, Taipei, Taiwan 7 Department of Life Science, Fu Jen Catholic University, Taipei, Taiwan 8 Department of Stem Cell Research, Cosmetic Clinic Group, Taipei, Taiwan 9 Graduate Institute of Basic Medicine, Fu Jen Catholic University, Taipei, Taiwan 10 Department of Family Medicine, School of Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan 11 Department of Family Medicine, Taipei Medical University Hospital, Taipei, Taiwan Correspondence to: Win-Ping Deng, email: wpdeng@tmu.edu.tw Keywords: osteoarthritis (OA), immortalized bone marrow stem cells (iBMSCs), cartilage regeneration, human papilloma virus (HPV)-16 E6/E7, molecular imaging Received: July 14, 2017 Accepted: August 27, 2017 Published: September 27, 2017 ABSTRACT Pathophysiology of osteoarthritis (OA) is characterized by progressive loss of articular cartilage in the knee-joints. To impart regenerative ability in lowly metabolizing chondrocytes, the bone marrow stem cells (BMSCs) has recently been recognized as a superior alternative treatment for OA. However, study of primary BMSCs-mediated chondrogenesis is difficult due to progressive cellular aging and replicative senescence. To obtain a therapeutic cell population for OA, BMSCs were immortalized by human papilloma virus (HPV)-16 E6/E7 along with mCherry luciferase (mCL), a gene marker for non-invasive imaging, and designated as iBMSCs-mCL. Next, their cell morphology, population doubling time (PDT) and colony forming ability (CFU) were evaluated. Furthermore, pluripotency and immunophenotypic markers were investigated. To deduce therapeutic ability, iBMSCs-mCL were intra-articularly injected into right knee of anterior cruciate ligament transaction (ACLT)-OA mice model and tracked through non-invasive bioluminescence imaging. Cell morphology of iBMSCs-mCL was similar to parental BMSCs. PDT and CFU ability of iBMSCs-mCLs were significantly increased. Pluripotency and immunophenotypic markers were highly expressed in iBMSC-mCL. Long-term survival and tri-lineage differentiation particularly chondrogenic potential of iBMSCs-mCL were also demonstrated in vitro and then in vivo which was monitored through non-invasive imaging. Intensive bioluminescent signals in iBMSCs-mCL administered knee-joint indicated a marked in vivo survival and proliferation of iBMSCs-mCL. Immunohistochemical staining for type II collagen (IHC of Col II) and alcian blue & safranin o staining of proteoglycans also corroborated cartilage regeneration by iBMSCs-mCL. Conclusively, iBMSCs-mCL maintains stemness and in vivo cartilage regeneration potential suggesting a promising avenue for development of OA therapeutics.

Objective This study aimed to evaluate compliance with guidelines on hand hygiene by examining five handwashing categories in postgraduate year (PGY) dentists at a university teaching hospital and to evaluate the accuracy rates of handwashing. Methods Through direct observation, trained PGY dentists were monitored throughout their daily care routine of before contact with patients, before using an instrument, after contact with patients, upon direct exposure to patients’ fluids, and while touching the patients’ surrounding area. Hand hygiene opportunities were considered complete in each category. A total of 16,597 hand hygiene opportunities across 37 individuals were observed from July to October 2012 and from September to October 2013. Results The overall handwashing compliance rate was 34.7%. The handwashing compliance rate was higher during work in oral surgery services (92.8%) than during work in general clinical practice (34.2%). The accuracy rate of handwashing was also higher during work in oral surgery services (87.5%) than during work in general clinical practice (51.0%). Similar results were obtained across all five handwashing categories. Conclusions Handwashing compliance and accuracy rates are low in PGY dentists. More education and continuous monitoring are suggested to improve handwashing compliance, as well as the correct handwashing procedures for dentists.

Achievement of adequate implant stability is one of the determinants for long-term successful osseointegration. Resonance frequency analysis was developed to monitor implant stability and is now a well-recognized, non-invasive tool for determining the appropriate time for functional loading. However, there have been few studies with continuous evaluation and comparison of implant stability and marginal bone level changes between two different macro designs and clinical situations during the implant healing process. Thus, the purpose of this clinical trial is to evaluate the implant stability and marginal bone level changes of straight and conical implants during the implant healing process. In this prospective clinical trial, 25 participants were randomized to either straight or conical implants. A total of 32 titanium dental implants with a length of 9 mm or 11 mm were installed in the maxilla and the mandible according to the manufacturer’s instructions. A resonance frequency analyzer was used to measure the implant stability quotient (ISQ) at the time of implant placement and after 2 weeks, 4 weeks, 6 weeks, 8 weeks, 10 weeks, and 12 weeks of healing. The changes in the peri-implant marginal bone level were evaluated from digital radiographic films taken at the time of implant placement and after 4 weeks, 8 weeks, and 12 weeks of healing. The preliminary results of this study revealed higher ISQ values and better healing tendency for conical implants in comparison with straight implants in the maxilla. Similar ISQ values and healing tendency were observed for straight and conical implants in the mandible. No significant differences in marginal bone loss were found between the straight and conical implants. However, in the mandible, slightly more marginal bone loss was found with the conical implants than straight implants after 12 weeks of healing. In conclusion, ISQ healing tendency and marginal bone loss are influenced by implant macro-design and jaw regions. Straight implants revealed similar ISQ healing tendency and marginal bone loss in both the mandible and maxilla. Conical implants were confirmed more beneficial for maintenance of implant stability and marginal bone level in the maxilla.

Cancer is a leading cause of mortality and a major public health problem worldwide. For biological therapy against cancer, we previously developed a unique immunotherapeutic platform by combining mesenchymal stem cells with an antigen-specific protein vaccine. However, this system possesses a few limitations, such as improperly immortalized mesenchymal stem cells (MSCs) along with transfected oncogenic antigens in them. To overcome the limitations of this platform for future clinical application, we freshly prepared primary adipose-derived stem cells (ADSCs) and modified the E7&rsquo, antigen (E7&rsquo, ) as a non-oncogenic protein. Either subcutaneously co-inoculated with cancer cells or systemically administered after tumor growth, ADSC labeled with enhanced green fluorescent protein (eGFP) and combined with modified E7&rsquo, (ADSC-E7&rsquo, eGFP) cells showed significant antitumor activity when combined with the protein vaccine in both colon and lung cancer in mice. Specifically, this combined therapy inhibited tumor through inducing cell apoptosis. The significantly reduced endothelial cell markers, CD31 and vascular endothelial growth factor (VEGF), indicated strongly inhibited tumor angiogenesis. The activated immune system was demonstrated through the response of CD4+ T and natural killer (NK) cells, and a notable antitumor activity might be contributed by CD8+ T cells. Conclusively, these evidences imply that this promising immunotherapeutic platform might be a potential candidate for the future clinical application against cancer.

Objectives To quantify the effect of oral potentially malignant disorder (OPMD) subtypes on mortality from oral cancer and type 2 diabetes among areca nut chewers and/or cigarette smokers. Materials and methods A retrospective cohort design was devised to follow 14,749 men attending community-based screening program for oral cancer between 1998 and 2000 and followed until 2010. The Cox proportional hazards regression model was applied to assess the effect of OPMD on death. Results A total of 1,291(8.75%) patients were detected as OPMD. Among those free of T2DM at baseline, the elevated risk for death from T2DM was noted for OSF (aHR = 3.62, 95% CI: 1.25-10.51) and erythroplakia (aHR = 5.01, 95% CI: 1.17-21.45). The elevated risk for all-cause death for OPMD was mainly explained by deaths from oral cancer and T2DM but not other causes of death. Conclusions Oral potentially malignant disorder, particularly OSF and erythroplakia, in male cigarette smokers and/or areca nut chewers led to an incremental elevated risk of T2DM mortality in the way of being distal to the occurrence of T2DM, implying that early detection and prevention of OPMD may not only reduce oral cancer mortality but also result in the reduction of T2DM mortality.

Lei Qin,1,* Yi-Wei Kao,2,* Yueh-Lung Lin,3 Bou-Yue Peng,4 Win-Ping Deng,5 Tsung-Ming Chen,6 Kuan-Chou Lin,7 Kevin Sheng-Po Yuan,8 Alexander TH Wu,9 Ben-Chang Shia,10 Szu-Yuan Wu11–14 1School of Statistics, University of International Business and Economics, Beijing, China; 2Graduate Institute of Business Administration, Fu Jen Catholic University, Taipei, Taiwan; 3School of Mathematical Sciences, University of Nottingham, Ningbo, China; 4Department of Dentistry, Taipei Medical University Hospital, Taipei, Taiwan; 5Graduate Institute of Biomedical Materials and Engineering, Taipei Medical University, Taipei, Taiwan; 6Department of Otorhinolaryngology, Shuang-Ho Hospital, Taipei Medical University, Taipei, Taiwan; 7Department of Oral and Maxillofacial Surgery, Wan Fang Hospital, Taipei Medical University, Taipei, Taiwan; 8Department of Otorhinolaryngology, Wan Fang Hospital, Taipei Medical University, Taipei, Taiwan; 9PhD Program for Translational Medicine, Taipei Medical University, Taipei, Taiwan; 10College of Management, Taipei Medical University, Taipei, Taiwan; 11Institute of Clinical Science, Zhongshan Hospital, Fudan University, Shanghai, China; 12Department of Radiation Oncology, Wanfang Hospital, Taipei Medical University, Taipei, Taiwan; 13Department of Internal Medicine, School of Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan; 14Epidemiology and Bioinformatics Center, Wanfang Hospital, Taipei Medical University, Taipei, Taiwan *These authors contributed equally to this work Background: Few studies have evaluated the risk of oral cavity cancer (OC) in patients with recurrent oral aphthae (ROA) and dry eye syndrome (DES). This study assessed the risk of OC in patients who had received diagnoses of ROA and DES in Taiwan.Methods: A population-based frequency-matched case–control study was conducted in which data were analyzed from the National Health Insurance Research Database of Taiwan. Patients with ROA and DES were identified as the case cohort. Patients and controls without ROA and DES were frequency matched (1:4) on the basis of age, sex, monthly income, geographical location, and urbanization level. Chi-squared tests were conducted to compare demographic factor distributions between the patients and controls. Cox proportional hazards models were used to calculate the adjusted hazard ratios (aHRs) and 95% CI of OC diagnoses among the patients and controls. Risk consistency between the two cohorts was determined using subgroup analysis.Results: A total of 7,110 patients with ROA and DES and 28,388 controls were identified. The OC risk was significantly higher for female patients than controls (aHR=3.41, 95%CI=1.69–6.86). Furthermore, women aged 50–69 years exhibited a higher risk of OC than those in the other age groups. Female patients aged 50–59 years exhibited the highest aHR for OC (aHR=5.56, 95%CI=1.70–18.25), followed by those aged 60–69 years (aHR=4.34, 95%CI=1.26–15.99).Conclusion: ROA and DES may be associated with a high risk of OC in elderly women. Keywords: risk factor, oral cavity cancer, recurrent oral aphthae, dry eye syndrome, women

Pathophysiology of osteoarthritis (OA) is characterized by progressive loss of articular cartilage in the knee-joints. To impart regenerative ability in lowly metabolizing chondrocytes, the bone marrow stem cells (BMSCs) has recently been recognized as a superior alternative treatment for OA. However, study of primary BMSCs-mediated chondrogenesis is difficult due to progressive cellular aging and replicative senescence. To obtain a therapeutic cell population for OA, BMSCs were immortalized by human papilloma virus (HPV)-16 E6/E7 along with mCherry luciferase (mCL), a gene marker for non-invasive imaging, and designated as iBMSCs-mCL. Next, their cell morphology, population doubling time (PDT) and colony forming ability (CFU) were evaluated. Furthermore, pluripotency and immunophenotypic markers were investigated. To deduce therapeutic ability, iBMSCs-mCL were intra-articularly injected into right knee of anterior cruciate ligament transaction (ACLT)-OA mice model and tracked through non-invasive bioluminescence imaging. Cell morphology of iBMSCs-mCL was similar to parental BMSCs. PDT and CFU ability of iBMSCs-mCLs were significantly increased. Pluripotency and immunophenotypic markers were highly expressed in iBMSC-mCL. Long-term survival and tri-lineage differentiation particularly chondrogenic potential of iBMSCs-mCL were also demonstrated in vitro and then in vivo which was monitored through non-invasive imaging. Intensive bioluminescent signals in iBMSCs-mCL administered knee-joint indicated a marked in vivo survival and proliferation of iBMSCs-mCL. Immunohistochemical staining for type II collagen (IHC of Col II) and alcian blue & safranin o staining of proteoglycans also corroborated cartilage regeneration by iBMSCs-mCL. Conclusively, iBMSCs-mCL maintains stemness and in vivo cartilage regeneration potential suggesting a promising avenue for development of OA therapeutics.

NSC 95397, a quinone-based small molecule compound, has been identified as an inhibitor for dual-specificity phosphatases, including mitogen-activated protein kinase phosphatase-1 (MKP-1). MKP-1 is known to inactivate mitogen-activated protein kinases by dephosphorylating both of their threonine and tyrosine residues. Moreover, owing to their participation in tumorigenesis and drug resistance in colon cancer cells, MKP-1 is an attractive therapeutic target for colon cancer treatment. We therefore investigated the inhibitory activity of NSC 95397 against three colon cancer cell lines including SW480, SW620, and DLD-1, and their underlying mechanisms. The results demonstrated that NSC 95397 reduced cell viability and anchorage-independent growth of all the three colon cancer cell lines through inhibited proliferation and induced apoptosis via regulating cell-cycle-related proteins, including p21, cyclin-dependent kinases, and caspases. Besides, by using mitogen-activated protein kinase kinase (MEK)/extracellular signal-regulated kinase (ERK) inhibitor U0126, we provided mechanistic evidence that the antineoplastic effects of NSC 95397 were achieved via inhibiting MKP-1 activity followed by ERK1/2 phosphorylation. Conclusively, our results indicated that NSC 95397 might serve as an effective therapeutic intervention for colon cancer through regulating MKP-1 and ERK1/2 pathway.

In this study, an optimal selective laser melting (SLM) process for manufacturing dense NiTi alloy with pseudoelasticity and shape-memory capability was proposed. The microstructure, phase-transformation temperature, shape memory capability, and pseudoelasticity were investigated by scanning electron microscopy, X-ray diffraction, differential scanning calorimetry, and bending and tensile tests. NiTi powder with a particle size > 45 μm was selected for the subsequent SLM process, because it exhibited a Ni/Ti ratio of ~1 and a lower oxygen content than powders with smaller particle sizes. A thin-walled disk (0.48 mm thick) and cuboid samples (5 mm thick) were prepared for investigating the variation in the homogeneity of the microstructure. The thin-walled SLM-NiTi sample exhibited a marginally inhomogeneous microstructure between layers, and defects existed in the previously formed side. The cuboid SLM-NiTi sample was fabricated without undesirable secondary phases, and it exhibited a 100% shape-recovery rate under 2% bending strain and completely pseudoelastic under 3% strain. Also, the SLM-NiTi exhibited lower phase-transformation temperatures and a broader phase-transformation range than the original NiTi. The phase-transformation range can be reduced by annealing.

In this study, the wound healing properties of the gelatin-based hydrogel (GBH) wound dressing combined with adipose-derived stem cells (ADSCs) were investigated using the mouse and porcine models. The analytical results showed that the ADSCs harvested from the porcine significantly increased cell growth and promoted cell differentiation (adipogenesis and osteogenesis) in comparison to the ADSCs harvested from the mouse in vitro. Moreover, the in vivo results also indicated that the GBH wound dressing combined with ADSCs and its culture medium could potentially accelerate wound healing in the mouse and porcine models. The ADSCs presented a possibility of recovery from wounds and injuries through skin regeneration. Therefore, both in vitro and in vivo results demonstrated that the ADSCs can potentially be an effective clinical treatment through the GBH wound dressing, which is a promising evidence-based complementary and alternative medicine for skin regeneration. © 2018 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 107B: 278-285, 2019.

Pathophysiology of osteoarthritis (OA) is characterized by progressive loss of articular cartilage in the knee-joints. To impart regenerative ability in lowly metabolizing chondrocytes, the bone marrow stem cells (BMSCs) has recently been recognized as a superior alternative treatment for OA. However, study of primary BMSCs-mediated chondrogenesis is difficult due to progressive cellular aging and replicative senescence. To obtain a therapeutic cell population for OA, BMSCs were immortalized by human papilloma virus (HPV)-16 E6/E7 along with mCherry luciferase (mCL), a gene marker for non-invasive imaging, and designated as iBMSCs-mCL. Next, their cell morphology, population doubling time (PDT) and colony forming ability (CFU) were evaluated. Furthermore, pluripotency and immunophenotypic markers were investigated. To deduce therapeutic ability, iBMSCs-mCL were intra-articularly injected into right knee of anterior cruciate ligament transaction (ACLT)-OA mice model and tracked through non-invasive bioluminescence imaging. Cell morphology of iBMSCs-mCL was similar to parental BMSCs. PDT and CFU ability of iBMSCs-mCLs were significantly increased. Pluripotency and immunophenotypic markers were highly expressed in iBMSC-mCL. Long-term survival and tri-lineage differentiation particularly chondrogenic potential of iBMSCs-mCL were also demonstrated

Adipose-derived stem cells (ADSCs) are multipotent cells that have attracted much recent attention and emerged as therapeutic approaches in several medical fields. Although current knowledge of the biological impacts of ADSCs in cancer research is greatly improved, the underlying effects of ADSCs in tumor development remain controversial and cause the safety concerns in clinical utilization. Hence, we isolated primary ADSCs from the abdominal fat of mice and conducted interaction of ADSCs with Lewis lung carcinoma cells in culture and in mice to investigate the impacts of ADSCs on tumor development. Cytokine array and neutralizing antibody were further utilized to identify the key regulator and downstream signaling pathway. In this study, we demonstrated that ADSCs enhance the malignant characteristics of LLC1 cells, including cell growth ability and especially cancer stem cell property. ADSCs were then identified to promote tumor formation and growth in mice. We further determined that ADSC interaction with LLC1 cells stimulates increased secretion of interleukin-6 mainly from ADSCs, which then act in a paracrine manner on LLC1 cells to enhance their malignant characteristics. Interleukin-6 was also identified to regulate genes related to cell proliferation and cancer stem cell, as well as to activate JAK2/STAT3, a predominant interleukin-6-activated pathway, in LLC1 cells. Collectively, we demonstrated that ADSCs play a pro-malignant role in tumor development of Lewis lung carcinoma cells by particularly promoting cancer stem cell property through interleukin-6 paracrine circuit, which is important for safety considerations regarding the clinical application of ADSCs.

Background/purpose Poorly crystalline hydroxyapatite was improved so that it has better cell affinity in vitro . We studied the efficacy of a novel resorbable poorly crystalline hydroxyapatite-based biphasic calcium phosphate, BonaGraft, for bone regeneration in vivo . Materials and methods The beagle was used as an animal model, and cylindrical artificial bone defects (3 mm in diameter and 6 mm long) were produced in the alveolar bone. The BonaGraft (ratio of poorly crystalline hydroxyapatite to b-tricalcium phosphate, 60:40) was used to fill in the defect, and unfilled defects served as a control group. At 5, 8 and 10 weeks after the operation, the size of the residual graft and new bone formation were evaluation by a histomorphometric analysis. In a clinical trial, 33 enrolled patients included 15 males and 18 females with ages ranging from 35 to 54 years. The main indications were ridge augmentation ( n = 12), sinus lifting ( n = 2), repair of periodontal disease ( n = 14), and repair of radicular cysts ( n = 5). The clinical outcomes of the surgery were primarily evaluated by clinical radiographs. Results In the animal study, implanting BonaGraft produced greater new-bone formation (74.5% ± 1.0%) at 10 weeks postoperatively than that of the control (40.2% ± 0.3%). BonaGraft particles were gradually resorbed and substituted by bone. The in vivo graft resorption time and bone healing time of 12.1 weeks were mathematically determined by the least squares method. In the clinical test, all patients implanted with BonaGraft reported satisfactory clinical outcomes without major material-related side effects. According to the radiographic pictures, implantation of BonaGraft enhanced bone formation. Conclusion According to the animal study results, BonaGraft has a suitable resorption period and satisfactory outcomes of new bone formation. The clinical study produced high satisfaction with clinical results both objectively and subjectively. For this reason, BonaGraft seems to be an alternative choice for a bone substitute in dental applications.

Summary An odontogenic keratocyst is a histologically distinct lesion that is thought to arise from basal cells of the oral epithelium, usually occurring in the posterior portion of the mandible or the mandibular ramus. We report on a large odontogenic keratocyst that presented as nasal airway obstruction in a 6-year-old boy. To our knowledge, this is the youngest patient for whom a midline odontogenic keratocyst in the anterior maxillary region has been documented in the English literature. We designed a less-invasive surgical approach for transnasal endoscopic marsupialization instead of enucleation of this large pediatric odontogenic keratocyst.