Porphyromonas gingivalis lipopolysaccharide regulates cell proliferation, apoptosis, autophagy in esophageal squamous cell carcinoma via TLR4/MYD88/JNK pathway.

The study aimed to explore the impact and potential mechanism of Porphyromonas gingivalis lipopolysaccharide (LPS-PG) on esophageal squamous cell carcinoma (ESCC) cell behavior. ESCC cells from the Shanghai Cell Bank were used, and TLR4, MYD88, and JNK interference vectors were constructed using adenovirus. The cells were divided into six groups: Control, Model, Model + radiotherapy + LPS-PG, Model + radiotherapy + 3-MA, Model + radiotherapy + LPS-PG + 3-MA, and Model + radiotherapy. Various radiation doses were applied to determine the optimal dose, and a radioresistant ESCC cell model was established and verified. CCK8 assay measured cell proliferation, flow cytometry and Hoechst 33258 assay assessed apoptosis, and acridine orange fluorescence staining tested autophagy. Western blot analyzed the expression of LC3II, ATG7, P62, and p-ULK1. Initially, CCK8 and acridine orange fluorescence staining identified optimal LPS-PG intervention conditions. Results revealed that 10 ng/ml LPS-PG for 12 h was optimal. LPS-PG increased autophagy activity, while 3-MA decreased it. LPS-PG + 3-MA group exhibited reduced autophagy. LPS-PG promoted proliferation and autophagy, inhibiting apoptosis in radioresistant ESCCs. LPS-PG regulated TLR4/MYD88/JNK pathway, enhancing ESCC autophagy, proliferation, and radioresistance. In conclusion, LPS-PG, through the TLR4/MYD88/JNK pathway, promotes ESCC proliferation, inhibits apoptosis, and enhances radioresistance by inducing autophagy.

A cross-sectional survey of attitudes and barriers toward pharmacist services at predoctoral academic dental institutions.

BACKGROUND: The pharmacy profession continues to evolve through novel practice settings and collaborations. Recent reports have highlighted services provided by pharmacists in academic dental settings. OBJECTIVES: This study aimed to measure attitudes and barriers to pharmacist services at academic dental institutions via a survey of dental school administrators. METHODS: A survey was circulated in summer 2019 to all accredited dental schools in the United States through the American Dental Education Association clinic dean listserv. The survey consisted of Likert scale questions pertaining to barriers and attitudes regarding pharmacist services in dental education programs and clinics. The survey was open from July 2019 to December 2019. Responses were analyzed with descriptive statistics and Spearman rank correlation. RESULTS: Complete attitude and barrier responses were received from 30 of 66 accredited institutions. Responding schools showed a generally positive attitude toward pharmacist services. Respondents identified funding as the barrier with greatest impact on program development and expansion. CONCLUSION: Attitudes among dental education program administrators regarding pharmacists are generally positive. Barriers remain to fully incorporating pharmacists into dental institutions in the United States. Increased funding and reimbursement for pharmacy services would support universal pharmacist integration to this practice setting.

[Community Innovation and Regional Sustainability: A Case Study on an Elder Social Survey Conducted by National Cheng Kung University].

National Cheng Kung University (NCKU) promotes university social responsibility and strives to ensure that all of its teaching staff and students engage in academics in a manner that incorporates both social awareness and social practice. The NCKU team has launched a series of social practice and research projects focused on accompanying and caring for older adults who live in the community, looking to establish a social practice model that bridges university teaching and research to practical community needs. The objective of this initiative is to develop an innovative model of social support and a new model for younger generations to work with older adults living in the community. The results of this survey project show better well-being in older adults to be associated with the following sets of traits: exercising regularly and lacking dental problems; engaging in daily laughter and holding positive aging perceptions; and having a higher subjective social status, more family support, and a sense of community attachment. The study results imply that multiple factors affect well-being in the context of caring for community-dwelling older adults and social development, especially during the current COVID-19 pandemic.

Medication Use Among Patients Reporting Xerostomia of an Academic Dental Clinic.

Background: Global prevalence of xerostomia has been reported at 22% (range 0.01%-45%), negatively impacting oral health, nutrition intake, and quality of life. The causal relationship between xerostomia and medications remains uncertain but greater understanding could guide interventions. Objective: To describe the demographic characteristics and medication regimens in patients with xerostomia of an academic dental clinic. Method: This is a retrospective academic dental clinic record review from July 1, 2018 to October 27, 2020. Patient records were obtained from the University at Buffalo, School of Dental Medicine. Xerostomia status was determined via query of electronic health records and validated by manual review. Pharmacologic class and xerostomic potential of medications were identified by the Veterans Affairs Drug Classification System and drug compendia, respectively. Predictors of medication use were assessed using a multiple logistic regression model. Results: Of 37 403 examined records, 366 (0.98%) were identified as xerostomic. After excluding confounding factors (Sjogren's and radiation), 275 of 317 patients received at least one xerostomic medication, majority were female (240, 66%) versus male (126, 34%). Mean ± (SD) age was 64.9 ± 15.11 years. A total of 208 (57%) patients were aged ≥65. The median number of total and xerostomic medications were 8 (interquartile range [IQR], 4-12) and 4 (IQR, 2-7), respectively. The 3 most prevalent xerostomic pharmacologic classes were antidepressants (131, 35%), gastric medications (101, 28%), and vitamin D (87, 24%). Conclusion: Despite observed prevalence of xerostomia lower than global prevalence, xerostomic medication burden for patients experiencing xerostomia was high. Pharmacist-led interprofessional collaborations should be investigated to reduce xerostomic burden.

Electronic sensor and actuator webs for large-area complex geometry cardiac mapping and therapy.

Curved surfaces, complex geometries, and time-dynamic deformations of the heart create challenges in establishing intimate, nonconstraining interfaces between cardiac structures and medical devices or surgical tools, particularly over large areas. We constructed large area designs for diagnostic and therapeutic stretchable sensor and actuator webs that conformally wrap the epicardium, establishing robust contact without sutures, mechanical fixtures, tapes, or surgical adhesives. These multifunctional web devices exploit open, mesh layouts and mount on thin, bio-resorbable sheets of silk to facilitate handling in a way that yields, after dissolution, exceptionally low mechanical moduli and thicknesses. In vivo studies in rabbit and pig animal models demonstrate the effectiveness of these device webs for measuring and spatially mapping temperature, electrophysiological signals, strain, and physical contact in sheet and balloon-based systems that also have the potential to deliver energy to perform localized tissue ablation.

Concurrent Ingestion of Alkaline Water and L-Glutamine Enhanced Salivary α-Amylase Activity and Testosterone Concentration in Boxing Athletes.

Athletes often take sport supplements to reduce fatigue and immune disturbances during or after training. This study evaluated the acute effects of concurrent ingestion of alkaline water and L-glutamine on the salivary immunity and hormone responses of boxers after training. Twelve male boxing athletes were recruited in this study. During regular training, the participants were randomly divided into three groups and asked to consume 400 mL of alkaline water (Group A), 0.15 g/kg body weight of L-glutamine with 400 mL of water (Group G), and 0.15 g/kg of L-glutamine with 400 mL of alkaline water (Group A+G) at the same time each day for three consecutive weeks. Before and immediately after the training, saliva, heart rates, and the rate of perceived exertion were investigated. The activity of α-amylase and concentrations of lactoferrin, immunoglobulin A (IgA), testosterone, and cortisol in saliva were measured. The results showed that the ratio of α-amylase activity/total protein (TP) significantly increased after training in Group A+G but not in Group A or G, whereas the ratios of lactoferrin/TP and IgA/TP were unaffected in all three groups. The concentrations of salivary testosterone after training increased significantly in Group A+G but not in Group A or G, whereas the salivary cortisol concentrations were unaltered in all groups. In conclusion, concurrent ingestion of 400 mL of alkaline water and 0.15 g/kg of L-glutamine before training enhanced the salivary α-amylase activity and testosterone concentration of boxers, which would be beneficial for post-exercise recovery.

Supplementation of L-glutamine enhanced mucosal immunity and improved hormonal status of combat-sport athletes.

BACKGROUND: Maintaining proper immune function and hormone status is important for athletes to avoid upper respiratory tract infection (URTI) and insufficient recovery, which is detrimental to sport performance and health. The aim of this study was to evaluate whether three-week supplementation of L-glutamine could benefit the mucosal immunity and hormonal status of combat-sport athletes as well as their rates of upper respiratory tract infection (URTI) and subjective feelings of well-being after intensive training. METHODS: Twenty-one combat-sport athletes from the National Taiwan University of Sport were recruited in this study. After intensive training, two groups of the participants were asked to consume powder form of 0.3 g/kg body weight of L-glutamine (GLU group) or maltodextrin (PLA group) with drinking water in a randomized design at the same time every day during 3 weeks. Saliva samples were collected to measure immunoglobulin A (IgA), nitric oxide (NO), testosterone (T) and cortisol (C) before and after three-week supplementation; moreover, Hooper's index questionnaires were completed for wellness assessment. The incidence and duration of URTI were recorded by using a health checklist throughout the entire study period. RESULTS: Supplementation of L-glutamine significantly enhanced the concentrations of IgA and NO in saliva; additionally, the incidence of URTI was significantly reduced. Regarding hormones, T concentration was significantly decreased in the PLA group, whereas C concentration was significantly increased, resulting in a significant decrease of T/C ratio. In contrast, the GLU group showed a significant increase of T/C ratio, while the mood scores of the Hooper's index questionnaire were higher in the PLA group. CONCLUSIONS: Three-week supplementation of L-glutamine after intensive training enhanced the mucosal immunity, improved hormonal status and reduced the rate of URTI of combat-sport athletes while feelings of well-being were also enhanced. Therefore, L-glutamine would be beneficial for the sports performance and recovery of athletes.

An environmental scan of pharmacists supporting pre-doctoral dental education institutions.

PURPOSE/OBJECTIVES: Reports have described pharmacists providing services within academic dental settings. The full scope of these activities and where they exist is unreported. This environmental scan was performed to identify and summarize the levels in which pharmacists provide support to predoctoral dental education programs. METHODS: A survey was circulated in summer 2019 to all CODA accredited dental schools through the American Dental Education Association (ADEA) clinical dean listserv. The IRB approved survey consisted of 23 questions pertaining to the pharmacist's role in predoctoral dental education programs. Institutions were asked whether pharmacists were used and what kinds of services pharmacists provided. Pharmacist roles were classified into standard pharmacy services, clinical pharmacy services, medication inventory, education, and administration/research. Univariate analysis was performed on responses and reported using descriptive statistics. RESULTS: A response rate of 59.1% from 66 institutions was achieved. Of those responding, 28.21% reported utilizing a pharmacist at their institution. Of the institutions responding positively to utilizing a pharmacist, the most common standard pharmacy services used were patient counseling regarding a disease state (50%), and medication errors/adverse event reporting (60%). Some clinical pharmacy services provided were medication history collection (70%), advising antimicrobial selection (50%), and treatment plan consultation (60%). Pharmacists were also found to be active in education, school administration, and research. CONCLUSION: Pharmacists are utilized at just over a quarter of responding CODA accredited predoctoral dental education institutions in the United States. Where deployed, pharmacists provide a wide array of services.

Autophagy and apoptotic machinery caused by Polygonum cuspidatum extract in cisplatin­resistant human oral cancer CAR cells.

Polygonum cuspidatum (Hu Zhang) is a traditional Chinese medicine (TCM) and has been revealed to exert anticancer, anti­angiogenesis, anti­human immunodeficiency virus (HIV), anti­hepatitis B virus, anti­microbial, anti­inflammatory, and neuro­protective bio­activities. However, the effect of P. cuspidatum extract (PCE) on drug­resistant human oral cancer cells regarding cell death is not fully understood yet. The present study was undertaken to explore the induction of autophagic and apoptotic cell death and to investigate their underlying molecular mechanisms in PCE­treated cisplatin­resistant human oral cancer CAR cells. Our results revealed that PCE was determined via HPLC analytic method, and it was revealed that resveratrol may be a major compound in PCE. The data also demonstrated that PCE reduced CAR cell viability in a concentration­ and time­dependent response via an MTT assay. PCE had an extremely low toxicity in human normal gingival fibroblasts (HGF). Autophagic and apoptotic cell death was found after PCE treatment by morphological determination. PCE was revealed to induce autophagy as determined using acridine orange (AO), LC3­GFP, monodansylcadaverine (MDC) and LysoTracker Red staining in CAR cells. In addition, PCE was revealed to induce apoptosis in CAR cells via 4',6­diamidino­2­phenylindole (DAPI)/terminal deoxynucleotidyl transferase dUTP nick­end labeling (TUNEL) double staining. PCE significantly stimulated caspase­9 and ­3 activities as revealed using caspase activity assays. PCE markedly increased the protein levels of Atg5, Atg7, Atg12, Beclin­1, LC3, Bax and cleaved caspase­3, while it decreased the protein expression of Bcl­2 in CAR cells as determined by western blotting. In conclusion, our findings are the first to suggest that PCE may be potentially efficacious for the treatment of cisplatin­resistant human oral cancer.

(-)-Menthol inhibits WEHI-3 leukemia cells in vitro and in vivo.

(-)-Menthol ([1-alpha]-5-methyl-2-[1-methylethyl]-cyclohexanol), is a widely used flavoring ingredient in mouthwash, foods, toothpaste and cigarettes. The studies reported here revealed that (-)-menthol induced cytotoxicity against murine leukemia WEHI-3 cells in vitro in a dose-dependent manner. The effects of (-)-menthol on WEHI-3 cells in vivo (BALBIc mice) were also examined, and it was observed that the Mac-3 and CD11b markers were decreased, indicating inhibition of differentiation of the precursor of macrophage and granulocyte. The weights of liver and spleen samples from mice treated with (-)-menthol were found to be decreased compared to untreated animals.

Flexible and stretchable nanowire-coated fibers for optoelectronic probing of spinal cord circuits.

Studies of neural pathways that contribute to loss and recovery of function following paralyzing spinal cord injury require devices for modulating and recording electrophysiological activity in specific neurons. These devices must be sufficiently flexible to match the low elastic modulus of neural tissue and to withstand repeated strains experienced by the spinal cord during normal movement. We report flexible, stretchable probes consisting of thermally drawn polymer fibers coated with micrometer-thick conductive meshes of silver nanowires. These hybrid probes maintain low optical transmission losses in the visible range and impedance suitable for extracellular recording under strains exceeding those occurring in mammalian spinal cords. Evaluation in freely moving mice confirms the ability of these probes to record endogenous electrophysiological activity in the spinal cord. Simultaneous stimulation and recording is demonstrated in transgenic mice expressing channelrhodopsin 2, where optical excitation evokes electromyographic activity and hindlimb movement correlated to local field potentials measured in the spinal cord.

Paxillin facilitates timely neurite initiation on soft-substrate environments by interacting with the endocytic machinery.

Neurite initiation is the first step in neuronal development and occurs spontaneously in soft tissue environments. Although the mechanisms regulating the morphology of migratory cells on rigid substrates in cell culture are widely known, how soft environments modulate neurite initiation remains elusive. Using hydrogel cultures, pharmacologic inhibition, and genetic approaches, we reveal that paxillin-linked endocytosis and adhesion are components of a bistable switch controlling neurite initiation in a substrate modulus-dependent manner. On soft substrates, most paxillin binds to endocytic factors and facilitates vesicle invagination, elevating neuritogenic Rac1 activity and expression of genes encoding the endocytic machinery. By contrast, on rigid substrates, cells develop extensive adhesions, increase RhoA activity and sequester paxillin from the endocytic machinery, thereby delaying neurite initiation. Our results highlight paxillin as a core molecule in substrate modulus-controlled morphogenesis and define a mechanism whereby neuronal cells respond to environments exhibiting varying mechanical properties.

One-step optogenetics with multifunctional flexible polymer fibers.

Optogenetic interrogation of neural pathways relies on delivery of light-sensitive opsins into tissue and subsequent optical illumination and electrical recording from the regions of interest. Despite the recent development of multifunctional neural probes, integration of these modalities in a single biocompatible platform remains a challenge. We developed a device composed of an optical waveguide, six electrodes and two microfluidic channels produced via fiber drawing. Our probes facilitated injections of viral vectors carrying opsin genes while providing collocated neural recording and optical stimulation. The miniature (<200 µm) footprint and modest weight (<0.5 g) of these probes allowed for multiple implantations into the mouse brain, which enabled opto-electrophysiological investigation of projections from the basolateral amygdala to the medial prefrontal cortex and ventral hippocampus during behavioral experiments. Fabricated solely from polymers and polymer composites, these flexible probes minimized tissue response to achieve chronic multimodal interrogation of brain circuits with high fidelity.

Characterization of silk fibroin modified surface: a proteomic view of cellular response proteins induced by biomaterials.

The purpose of this study was to develop the pathway of silk fibroin (SF) biopolymer surface induced cell membrane protein activation. Fibroblasts were used as an experimental model to evaluate the responses of cellular proteins induced by biopolymer material using a mass spectrometry-based profiling system. The surface was covered by multiwalled carbon nanotubes (CNTs) and SF to increase the surface area, enhance the adhesion of biopolymer, and promote the rate of cell proliferation. The amount of adhered fibroblasts on CNTs/SF electrodes of quartz crystal microbalance (QCM) greatly exceeded those on other surfaces. Moreover, analyzing differential protein expressions of adhered fibroblasts on the biopolymer surface by proteomic approaches indicated that CD44 may be a key protein. Through this study, utilization of mass spectrometry-based proteomics in evaluation of cell adhesion on biopolymer was proposed.

3D multifunctional integumentary membranes for spatiotemporal cardiac measurements and stimulation across the entire epicardium.

Means for high-density multiparametric physiological mapping and stimulation are critically important in both basic and clinical cardiology. Current conformal electronic systems are essentially 2D sheets, which cannot cover the full epicardial surface or maintain reliable contact for chronic use without sutures or adhesives. Here we create 3D elastic membranes shaped precisely to match the epicardium of the heart via the use of 3D printing, as a platform for deformable arrays of multifunctional sensors, electronic and optoelectronic components. Such integumentary devices completely envelop the heart, in a form-fitting manner, and possess inherent elasticity, providing a mechanically stable biotic/abiotic interface during normal cardiac cycles. Component examples range from actuators for electrical, thermal and optical stimulation, to sensors for pH, temperature and mechanical strain. The semiconductor materials include silicon, gallium arsenide and gallium nitride, co-integrated with metals, metal oxides and polymers, to provide these and other operational capabilities. Ex vivo physiological experiments demonstrate various functions and methodological possibilities for cardiac research and therapy.

Curcumin-loaded nanoparticles induce apoptotic cell death through regulation of the function of MDR1 and reactive oxygen species in cisplatin-resistant CAR human oral cancer cells.

Curcumin is a polyphenolic compound which possesses anticancer potential. It has been shown to induce cell death in a variety of cancer cells, however, its effect on CAL27­cisplatin-resistant human oral cancer cells (CAR cells) has not been elucidated to date. The low water solubility of curcumin which leads to poor bioavailability, however, has been highlighted as a major limiting factor. In this study, we utilized water-soluble PLGA curcumin nanoparticles (Cur-NPs), and investigated the effects of Cur-NPs on CAR cells. The results showed Cur-NPs induced apoptosis in CAR cells but exhibited low cytotoxicity to normal human gingival fibroblasts (HGFs) and normal human oral keratinocytes (OKs). Cur-NPs triggered DNA concentration, fragmentation and subsequent apoptosis. Compared to untreated CAR cells, a more detectable amount of Calcein-AM accumulation was found inside the treated CAR cells. Cur-NPs suppressed the protein and mRNA expression levels of MDR1. Both the activity and the expression levels of caspase-3 and caspase-9 were elevated in the treated CAR cells. The Cur-NP-triggered apoptosis was blocked by specific inhibitors of pan-caspase (z-VAD-fmk), caspase-3 (z-DEVD-fmk), caspase-9 (z-LEHD-fmk) and antioxidant agent (N-acetylcysteine; NAC). Cur-NPs increased reactive oxygen species (ROS) production, upregulated the protein expression levels of cleaved caspase-3/caspase-9, cytochrome c, Apaf-1, AIF, Bax and downregulated the protein levels of Bcl-2. Our results suggest that Cur-NPs triggered the intrinsic apoptotic pathway through regulating the function of multiple drug resistance protein 1 (MDR1) and the production of reactive oxygen species (ROS) in CAR cells. Cur-NPs could be potentially efficacious in the treatment of cisplatin-resistant human oral cancer.