The utility of microbiome (microbiota) and exosomes in dentistry.

The concept of the oral-systemic link is important in both basic and clinical dentistry. The microbiome (microbiota) and exosomes are two prevalent issues in the modern medical researches. The common advent of oral and general microbiological investigation originated from the initial observations of oral bacteria within the dental plaque known as oral microbiome. In addition to oral diseases related to oral microbiome, the disruption of the oral and intestinal microbiome could result in the onset of systemic diseases. In the past decade, the exosomes have emerged in the field of the medical researches as they play a role in regulating the transport of intracellular vesicles. However, with the rapid advancement of exosomes researches in recent years, oral tissues (such as dental pulp stem cells and salivary gland cells) are used as the research materials to further promote the development of regenerative medicine. This article emphasized the importance of the concept of the oral-systemic link through the examples of microbiome (microbiota) and exosomes. Through the researches related to microbiome (microbiota) and exosomes, many evidences showed that as the basic dentistry developed directly from the assistance of the basic medicine, indirectly the progress of the basic dentistry turns back to promote the development of the basic medicine, indicating the importance of the concept of the oral-systemic link. The understanding of the oral-systemic link is essential for both clinicians and medical researchers, regardless of their dental backgrounds.

Ethnicity, gender, and geographical distribution of dentists in Taiwan in 1939 (Showa 14).

Background/purpose: Taiwan's dentistry entered into a new era of modernization and flourished during the Japanese colonial period. However, we know very little about the composition of dentists at that time. This study attempted to analyze the ethnicity, gender, and geographical distribution of dentists in Taiwan in 1939 (Showa 14). Materials and methods: The methods of documentary analysis and secondary data analysis were adopted to find the composition of dentists during the late Japanese colonial period through a name list of contract dentists for the Postal Savings Insurance published in August 1939 (Showa 14) by the Taiwan Government Transportation Department Information Bureau. Results: The total number of contract dentists was 368, accounting for 86.79% of the 424 practicing dentists in Taiwan in 1939 (Showa 14). Of the 368 contract dentists (328 males and 40 females), 225 (61.14%) were Taiwanese and 143 (38.86%) were Japanese. Among the 8 prefectures in Taiwan, Tainan Prefecture had the largest number of dentists (97), followed by Taipei (84) and Taichung (78) prefectures. The number of contract dentists per 100,000 people was 6.24, equivalent to 16,021 people served by each contract dentist in 1939 (Showa 14). The chi-square test for the trend analysis of gender distribution indicated a significantly higher proportion of male than female contract dentists in either Taiwanese or Japanese ethnic group. Conclusion: In the late Japanese colonial period, the number of Taiwanese dentists exceeded that of Japanese dentists. Furthermore, there were more male than female dentists in either the Taiwanese or the Japanese population.

The mechanisms of Porphyromonas gingivalis-derived outer membrane vesicles-induced neurotoxicity and microglia activation.

Background/purpose: Periodontitis is associated with various systemic diseases, potentially facilitated by the passage of Porphyromonas gingivalis outer membrane vesicles (Pg-OMVs). Several recent studies have suggested a connection between Pg-OMVs and neuroinflammation and neurodegeneration, but the precise causal relationship remains unclear. This study aimed to investigate the mechanisms underlying these associations using in vitro models. Materials and methods: Isolated Pg-OMVs were characterized by morphology, size, and gingipain activity. We exposed SH-SY5Y neuroblastoma cells and BV-2 microglial cells to various concentrations of Pg-OMVs. Cell morphology, a 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay, an enzyme-linked immunosorbent assay, and Western blot analysis were used to evaluate the cellular mechanism underlying Pg-OMV-induced neurotoxicity in neuronal cells and inflammatory responses in microglial cells. Results: Exposure to Pg-OMVs induced neurotoxicity in SH-SY5Y cells, as evidenced by cellular shrinkage, reduced viability, activation of apoptotic pathways, and diminished neuronal differentiation markers. Gingipain inhibition mitigated these effects, suggesting that gingipain mediates Pg-OMVs-induced neurotoxicity in SH-SY5Y cells. Our research on neuroinflammation suggests that upon endocytosis of Pg-OMVs by BV-2 cells, lipopolysaccharide (LPS) can modulate the production of inducible nitric oxide synthase and tumor necrosis factor-alpha by activating pathways that involve phosphorylated AKT and the phosphorylated JNK pathway. Conclusion: Our study demonstrated that following the endocytosis of Pg-OMVs, gingipain can induce neurotoxicity in SH-SY5Y cells. Furthermore, the Pg-OMVs-associated LPS can trigger neuroinflammation via AKT and JNK signaling pathways in BV-2 cells.

High-throughput screen identifies non inflammatory small molecule inducers of trained immunity.

Trained immunity is characterized by epigenetic and metabolic reprogramming in response to specific stimuli. This rewiring can result in increased cytokine and effector responses to pathogenic challenges, providing nonspecific protection against disease. It may also improve immune responses to established immunotherapeutics and vaccines. Despite its promise for next-generation therapeutic design, most current understanding and experimentation is conducted with complex and heterogeneous biologically derived molecules, such as ß-glucan or the Bacillus Calmette-Guérin (BCG) vaccine. This limited collection of training compounds also limits the study of the genes most involved in training responses as each molecule has both training and nontraining effects. Small molecules with tunable pharmacokinetics and delivery modalities would both assist in the study of trained immunity and its future applications. To identify small molecule inducers of trained immunity, we screened a library of 2,000 drugs and drug-like compounds. Identification of well-defined compounds can improve our understanding of innate immune memory and broaden the scope of its clinical applications. We identified over two dozen small molecules in several chemical classes that induce a training phenotype in the absence of initial immune activation-a current limitation of reported inducers of training. A surprising result was the identification of glucocorticoids, traditionally considered immunosuppressive, providing an unprecedented link between glucocorticoids and trained innate immunity. We chose seven of these top candidates to characterize and establish training activity in vivo. In this work, we expand the number of compounds known to induce trained immunity, creating alternative avenues for studying and applying innate immune training.

N, N-Dimethyltryptamine, a natural hallucinogen, ameliorates Alzheimer's disease by restoring neuronal Sigma-1 receptor-mediated endoplasmic reticulum-mitochondria crosstalk.

BACKGROUND: Aberrant neuronal Sigma-1 receptor (Sig-1r)-mediated endoplasmic reticulum (ER)- mitochondria signaling plays a key role in the neuronal cytopathology of Alzheimer's disease (AD). The natural psychedelic N, N-dimethyltryptamine (DMT) is a Sig-1r agonist that may have the anti-AD potential through protecting neuronal ER-mitochondrial interplay. METHODS: 3×TG-AD transgenic mice were administered with chronic DMT (2 mg/kg) for 3 weeks and then performed water maze test. The Aß accumulation in the mice brain were determined. The Sig-1r level upon DMT treatment was tested. The effect of DMT on the ER-mitochondrial contacts site and multiple mitochondria-associated membrane (MAM)-associated proteins were examined. The effect of DMT on calcium transport between ER and mitochondria and the mitochondrial function were also evaluated. RESULTS: chronic DMT (2 mg/kg) markedly alleviated cognitive impairment of 3×TG-AD mice. In parallel, it largely diminished Aß accumulation in the hippocampus and prefrontal cortex. DMT restored the decreased Sig-1r levels of 3×TG-AD transgenic mice. The hallucinogen reinstated the expression of multiple MAM-associated proteins in the brain of 3×TG-AD mice. DMT also prevented physical contact and calcium dynamic between the two organelles in in vitro and in vivo pathological circumstances. DMT modulated oxidative phosphorylation (OXPHOS) and ATP synthase in the in vitro model of AD. CONCLUSION: The anti-AD effects of DMT are associated with its protection of neuronal ER-mitochondria crosstalk via the activation of Sig-1r. DMT has the potential to serve as a novel preventive and therapeutic agent against AD.

Deep learning unlocks label-free viability assessment of cancer spheroids in microfluidics.

Despite recent advances in cancer treatment, refining therapeutic agents remains a critical task for oncologists. Precise evaluation of drug effectiveness necessitates the use of 3D cell culture instead of traditional 2D monolayers. Microfluidic platforms have enabled high-throughput drug screening with 3D models, but current viability assays for 3D cancer spheroids have limitations in reliability and cytotoxicity. This study introduces a deep learning model for non-destructive, label-free viability estimation based on phase-contrast images, providing a cost-effective, high-throughput solution for continuous spheroid monitoring in microfluidics. Microfluidic technology facilitated the creation of a high-throughput cancer spheroid platform with approximately 12 000 spheroids per chip for drug screening. Validation involved tests with eight conventional chemotherapeutic drugs, revealing a strong correlation between viability assessed via LIVE/DEAD staining and phase-contrast morphology. Extending the model's application to novel compounds and cell lines not in the training dataset yielded promising results, implying the potential for a universal viability estimation model. Experiments with an alternative microscopy setup supported the model's transferability across different laboratories. Using this method, we also tracked the dynamic changes in spheroid viability during the course of drug administration. In summary, this research integrates a robust platform with high-throughput microfluidic cancer spheroid assays and deep learning-based viability estimation, with broad applicability to various cell lines, compounds, and research settings.

Optical, Electrical, Structural, and Thermo-Mechanical Properties of Undoped and Tungsten-Doped Vanadium Dioxide Thin Films.

The undoped and tungsten (W)-doped vanadium dioxide (VO2) thin films were prepared by electron beam evaporation associated with ion-beam-assisted deposition (IAD). The influence of different W-doped contents (3-5%) on the electrical, optical, structural, and thermo-mechanical properties of VO2 thin films was investigated experimentally. Spectral transmittance results showed that with the increase in W-doped contents, the transmittance in the visible light range (400-750 nm) decreases from 60.2% to 53.9%, and the transmittance in the infrared wavelength range (2.5 µm to 5.5 µm) drops from 55.8% to 15.4%. As the W-doped content increases, the residual stress in the VO2 thin film decreases from -0.276 GPa to -0.238 GPa, but the surface roughness increases. For temperature-dependent spectroscopic measurements, heating the VO2 thin films from 30 °C to 100 °C showed the most significant change in transmittance for the 5% W-doped VO2 thin film. When the heating temperature exceeds 55 °C, the optical transmittance drops significantly, and the visible light transmittance drops by about 11%. Finally, X-ray diffraction (XRD) and scanning electron microscope (SEM) were used to evaluate the microstructure characteristics of VO2 thin films.

Predicting Lung Cancer Survival to the Future: Population-Based Cancer Survival Modeling Study.

BACKGROUND: Lung cancer remains the leading cause of cancer-related mortality globally, with late diagnoses often resulting in poor prognosis. In response, the Lung Ambition Alliance aims to double the 5-year survival rate by 2025. OBJECTIVE: Using the Taiwan Cancer Registry, this study uses the survivorship-period-cohort model to assess the feasibility of achieving this goal by predicting future survival rates of patients with lung cancer in Taiwan. METHODS: This retrospective study analyzed data from 205,104 patients with lung cancer registered between 1997 and 2018. Survival rates were calculated using the survivorship-period-cohort model, focusing on 1-year interval survival rates and extrapolating to predict 5-year outcomes for diagnoses up to 2020, as viewed from 2025. Model validation involved comparing predicted rates with actual data using symmetric mean absolute percentage error. RESULTS: The study identified notable improvements in survival rates beginning in 2004, with the predicted 5-year survival rate for 2020 reaching 38.7%, marking a considerable increase from the most recent available data of 23.8% for patients diagnosed in 2013. Subgroup analysis revealed varied survival improvements across different demographics and histological types. Predictions based on current trends indicate that achieving the Lung Ambition Alliance's goal could be within reach. CONCLUSIONS: The analysis demonstrates notable improvements in lung cancer survival rates in Taiwan, driven by the adoption of low-dose computed tomography screening, alongside advances in diagnostic technologies and treatment strategies. While the ambitious target set by the Lung Ambition Alliance appears achievable, ongoing advancements in medical technology and health policies will be crucial. The study underscores the potential impact of continued enhancements in lung cancer management and the importance of strategic health interventions to further improve survival outcomes.

Insights Into Colorectal Cancer Screening: A Multidatabase Cohort Study of Over 1.5 Million Taiwanese.

INTRODUCTION: Colorectal cancer (CRC) remains a significant public health concern. This study aims to provide a comprehensive understanding of the effectiveness of fecal immunochemical test (FIT) screening on CRC incidence and mortality, leveraging the scale of over 1.5 million randomly selected Taiwanese and more than 11.7 million person-years of follow-up. METHODS: This prospective cohort study merges data from 3 robust Taiwanese health databases: the CRC screening program, cancer registration, and death registration databases. Incidence and mortality rates of CRC were calculated based on age, sex, urbanization, and past screening status. Cox proportional hazard models were used to assess the association between screening statuses and CRC incidence or mortality, adjusting for age, sex, and urbanization levels. Statistical analysis of the data was conducted in 2021-2022. RESULTS: FIT screening was associated with a 33% reduction in CRC incidence and a 47% reduction in mortality. The study identified a dose-response relationship between the fecal hemoglobin concentration (f-HbC) levels and CRC risk. Participants with consistent FIT-negative results had significantly reduced CRC incidence and mortality risks, while those with one or more positive FIT results faced increased risks. Notably, compliance with follow-up examinations after a positive FIT significantly lowered mortality risk. CONCLUSIONS: This large-scale study validates the efficacy of FIT screening in reducing CRC incidence and mortality. It offers a nuanced understanding of how various screening statuses impact CRC risks, thus providing valuable insights for public health strategies aimed at CRC prevention.

A nationwide case-referent study on elevated risks of adenocarcinoma lung cancer by long-term PM2.5 exposure in Taiwan since 1997.

BACKGROUND: The effects of long-term PM2.5 exposures since 1968 on adenocarcinoma lung cancer (AdLC) were not studied before. METHODS: This case-referent study used nationwide cancer registry data since 1997 and air pollution data since 1968 in Taiwan to estimate risks of 30-year PM2.5 exposures on AdLC. Cases were all AdLC, while references were all non-AdLC. Individuals' 30-year PM2.5 exposures were estimated by PM2.5 levels at their residence for 30 years prior their diagnosis dates. We applied multiple logistic regression analyses to estimate PM2.5 exposures on incidence rate ratios (IRRs) between cases and references, adjusting for sex, age, smoking, cancer stage, and EGFR mutation. RESULTS: Elevation in annual ambient PM2.5 concentrations since 1968 were associated with increase in annual age-adjusted AdLC incidence since 1997. AdLC incidences were higher among females, nonsmokers, the elderly aged above 65, cases of stages IIIB to IV, and EGFR mutation. Study subjects' PM2.5 exposures averaged at 33.7 ± 7.4 µg/m3 with 162 ± 130 high PM2.5 pollution days over 30 years. Multiple logistic models showed an increase in 10 µg/m3 of PM2.5 exposures were significantly associated with 1.044 of IRR between all AdLC and all non-AdLC cases during 2011-2020. Our models also showed that females and nonsmokers and adults less than 65 years had higher IRRs than their respective counterparts. Restricted analyses showed similar effects of PM2.5 exposures on IRRs between stage 0-IIIA and IIIB-IV cases and between EGFR+ and EGFR- cases. CONCLUSIONS: Long-term exposures to PM2.5 over 30 years were associated with elevated risks of AdLC against non-AdLC, regardless of gender, age, smoking status, cancer stage, or EGFR mutation.