Heterogeneous Integration of Memristive and Piezoresistive MDMO-PPV-Based Copolymers in Nociceptive Transmission with Fast and Slow Pain for an Artificial Pain-Perceptual System.

Nociceptive pain perception is a remarkable capability of organisms to be aware of environmental changes and avoid injury, which can be accomplished by specialized pain receptors known as nociceptors with 4 vital properties including threshold, no adaptation, relaxation, and sensitization. Bioinspired systems designed using artificial devices are investigated to imitate the efficacy and functionality of nociceptive transmission. Here, an artificial pain-perceptual system (APPS) with a homogeneous material and heterogeneous integration is proposed to emulate the behavior of fast and slow pain in nociceptive transmission. Retention-differentiated poly[2-methoxy-5-(3,7-dimethyoctyoxyl)-1,4-phenylenevinylene] (MDMO-PPV) memristors with film thicknesses of 160 and 80 nm are manufactured and adopted as A-δ and C nerve fibers of nociceptor conduits, respectively. Additionally, a nociceptor mimic, the ruthenium nanoparticles (Ru-NPs)-doped MDMO-PPV piezoresistive pressure sensor, is fabricated with a noxiously stimulated threshold of 150 kPa. Under the application of pricking and dull noxious stimuli, the current flows predominantly through the memristor to mimic the behavior of fast and slow pain, respectively, in nociceptive transmission with postsynaptic potentiation properties, which is analogous to biological pain perception. The proposed APPS can provide potential advancements in establishing the nervous system, thus enabling the successful development of next-generation neurorobotics, neuroprosthetics, and precision medicine.

The Role of NRF2 in Trinucleotide Repeat Expansion Disorders.

Trinucleotide repeat expansion disorders, a diverse group of neurodegenerative diseases, are caused by abnormal expansions within specific genes. These expansions trigger a cascade of cellular damage, including protein aggregation and abnormal RNA binding. A key contributor to this damage is oxidative stress, an imbalance of reactive oxygen species that harms cellular components. This review explores the interplay between oxidative stress and the NRF2 pathway in these disorders. NRF2 acts as the master regulator of the cellular antioxidant response, orchestrating the expression of enzymes that combat oxidative stress. Trinucleotide repeat expansion disorders often exhibit impaired NRF2 signaling, resulting in inadequate responses to excessive ROS production. NRF2 activation has been shown to upregulate antioxidative gene expression, effectively alleviating oxidative stress damage. NRF2 activators, such as omaveloxolone, vatiquinone, curcumin, sulforaphane, dimethyl fumarate, and resveratrol, demonstrate neuroprotective effects by reducing oxidative stress in experimental cell and animal models of these diseases. However, translating these findings into successful clinical applications requires further research. In this article, we review the literature supporting the role of NRF2 in the pathogenesis of these diseases and the potential therapeutics of NRF2 activators.

Impact of comorbidities on relapsing rates of Neuromyelitis Optica Spectrum Disorders: Insights from a longitudinal study in Taiwan.

BACKGROUND: Neuromyelitis optica spectrum disorder (NMOSD) is an autoimmune inflammatory demyelinating disease characterized by relapsing clinical episodes and the presence of autoantibodies. The impact of comorbidities on relapsing rate of NMOSD patients in Taiwan remains unclear. METHODS: We conducted a longitudinal retrospective study using the largest hospital system in Taiwan from 2006 to 2021. Demographic characteristics, annualized relapse rates (ARR), and comorbidities were examined. RESULTS: We identified 485 NMOSD patients from 2006 to 2021. Of these, 466 had the adult form and 19 (3.9 %) had the pediatric form of NMOSD. The median ARR was 0.51 (interquartile range (IQR): 0.26-1.11) for adults and 0.39 (IQR: 0.21-0.77) for pediatric patients. Comorbidities included malignancy (6.7 %) and autoimmune diseases (21.7 %). The recommended age for malignancy surveillance in NMOSD patients was 43.3 years. Neither malignancy nor autoimmune disease increased the ARR within 3 years post diagnosis in NMOSD patients with comorbidities compared with those without comorbidities. CONCLUSIONS: Our study revealed the ARR within the initial three years after diagnosis was significantly higher, emphasizing the importance of early treatment. We also observed an association between malignancy and NMOSD, and a significantly higher risk of malignancy in adult patients with NMOSD than in the general population (the relative risk was 5.99) that requiring further investigations into the underlying mechanisms. These findings contribute to a better understanding of NMOSD and its comorbidities in Taiwan.

NT-proBNP point-of-care testing for predicting mortality in end-stage renal disease: A survival analysis.

This study examines the predictive value of elevated N-terminal-pro brain natriuretic peptide (NT-pro BNP) levels for mortality among patients with end-stage renal disease (ESRD). Data from 768 ESRD patients, excluding those with cancer or lost follow-up, were analyzed using Kaplan-Meier curves and Cox proportional hazards models over three years. Results indicated that patients with very high NT-pro BNP levels had shorter average survival times and a significantly higher risk of mortality (hazard ratio 1.43). Advanced age, ICU admission, and comorbidities like cerebrovascular diseases and chronic obstructive pulmonary disease also contributed to increased mortality risks. Thus, elevated NT-pro BNP is an independent risk factor for mortality in ESRD patients.

A traffic-induced shift of ultrafine particle sources under COVID-19 soft lockdown in a subtropical urban area.

During the unprecedented COVID-19 city lockdown, a unique opportunity arose to dissect the intricate dynamics of urban air quality, focusing on ultrafine particles (UFPs) and volatile organic compounds (VOCs). This study delves into the nuanced interplay between traffic patterns and UFP emissions in a subtropical urban setting during the spring-summer transition of 2021. Leveraging meticulous roadside measurements near a traffic nexus, our investigation unravels the intricate relationship between particle number size distribution (PNSD), VOCs mixing ratios, and detailed vehicle activity metrics. The soft lockdown era, marked by a 20-27% dip in overall traffic yet a surprising surge in early morning motorcycle activity, presented a natural experiment. We observed a consequential shift in the urban aerosol regime: the decrease in primary emissions from traffic substantially amplified the role of aged particles and secondary aerosols. This shift was particularly pronounced under stagnant atmospheric conditions, where reduced dilution exacerbated the influence of alternative emission sources, notably solvent evaporation, and was further accentuated with the resumption of normal traffic flows. A distinct seasonal trend emerged as warmer months approached, with aromatic VOCs such as toluene, ethylbenzene, and xylene not only increasing but also significantly contributing to more frequent particle growth events. These findings spotlight the criticality of targeted strategies at traffic hotspots, especially during periods susceptible to weak atmospheric dilution, to curb UFP and precursor emissions effectively. As we stand at the cusp of widespread vehicle electrification, this study underscores the imperative of a holistic approach to urban air quality management, embracing the complexities of primary emission reductions and the resultant shifts in atmospheric chemistry.

Protective Effects of Coptis chinensis Rhizome Extract and Its Constituents (Berberine, Coptisine, and Palmatine) against α-Synuclein Neurotoxicity in Dopaminergic SH-SY5Y Cells.

Parkinson's disease (PD) is a common neurodegenerative disease with progressive loss of dopaminergic neurons in substantia nigra and the presence of α-synuclein-immunoreactive inclusions. Gaucher's disease is caused by homozygous mutations in ß-glucocerebrosidase gene (GBA). GBA mutation carriers have an increased risk of PD. Coptis chinensis (C. chinensis) rhizome extract is a major herb widely used to treat human diseases. This study examined the association of GBA L444P mutation with Taiwanese PD in 1016 cases and 539 controls. In addition, the protective effects of C. chinensis rhizome extract and its active constituents (berberine, coptisine, and palmatine) against PD were assayed using GBA reporter cells, LC3 reporter cells, and cells expressing mutated (A53T) α-synuclein. Case-control study revealed that GBA L444P carriers had a 3.93-fold increased risk of PD (95% confidence interval (CI): 1.37-11.24, p = 0.006) compared to normal controls. Both C. chinensis rhizome extract and its constituents exhibited chemical chaperone activity to reduce α-synuclein aggregation. Promoter reporter and endogenous GBA protein analyses revealed that C. chinensis rhizome extract and its constituents upregulated GBA expression in 293 cells. In addition, C. chinensis rhizome extract and its constituents induced autophagy in DsRed-LC3-expressing 293 cells. In SH-SY5Y cells expressing A53T α-synuclein, C. chinensis rhizome extract and its constituents reduced α-synuclein aggregation and associated neurotoxicity by upregulating GBA expression and activating autophagy. The results of reducing α-synuclein aggregation, enhancing GBA expression and autophagy, and protecting against α-synuclein neurotoxicity open up the therapeutic potentials of C. chinensis rhizome extract and constituents for PD.

Digital Twin Meets Knowledge Graph for Intelligent Manufacturing Processes.

In the highly competitive field of material manufacturing, stakeholders strive for the increased quality of the end products, reduced cost of operation, and the timely completion of their business processes. Digital twin (DT) technologies are considered major enablers that can be deployed to assist the development and effective provision of manufacturing processes. Additionally, knowledge graphs (KG) have emerged as efficient tools in the industrial domain and are able to efficiently represent data from various disciplines in a structured manner while also supporting advanced analytics. This paper proposes a solution that integrates a KG and DTs. Through this synergy, we aimed to develop highly autonomous and flexible DTs that utilize the semantic knowledge stored in the KG to better support advanced functionalities. The developed KG stores information about materials and their properties and details about the processes in which they are involved, following a flexible schema that is not domain specific. The DT comprises smaller Virtual Objects (VOs), each one acting as an abstraction of a single step of the Industrial Business Process (IBP), providing the necessary functionalities that simulate the corresponding real-world process. By executing appropriate queries to the KG, the DT can orchestrate the operation of the VOs and their physical counterparts and configure their parameters accordingly, in this way increasing its self-awareness. In this article, the architecture of such a solution is presented and its application in a real laser glass bending process is showcased.

The upregulation of VGF enhances the progression of oral squamous carcinoma.

BACKGROUND: Oral squamous cell carcinoma (OSCC) is a prevalent neoplasm worldwide, necessitating a deeper understanding of its pathogenesis. VGF nerve growth factor inducible (VGF), a neuropeptide, plays critical roles in nerve and endocrine cell regulation. METHODS: In this study, the TCGA datasets were initially screened, identifying the upregulation of VGF in various malignancies. We focused on OSCC cell lines, identifying the suppressor mRNA miR-432-5p as a negative regulator of VGF. Additionally, we examined the prognostic value of VGF expression in OSCC tumors and its impact on cellular functions. RESULTS: VGF expression was found to be an independent prognostic predictor in OSCC tumors. Cells expressing VGF exhibited increased oncogenicity, influencing the proliferation and migration of oral mucosal fibroblast. Transcriptome analysis revealed associations between VGF and various pathological processes, including malignancies, exosome release, fibrosis, cell cycle disruption, and tumor immune suppression. Moreover, IL23R expression, a favorable OSCC prognostic factor, was inversely correlated with VGF expression. Exogenous IL23R expression was found to suppress VGF-associated mobility phenotypes. CONCLUSIONS: This study highlights the multifaceted role of VGF in OSCC pathogenesis and introduces the miR-432-5p-VGF-IL23R regulatory axis as a critical mediator. The combined expression of VGF and IL23R emerges as a potent predictor of survival in oral carcinoma cases, suggesting potential implications for future therapeutic strategies.

Investigating the therapeutic effects of novel compounds targeting inflammatory IL-1ß and IL-6 signaling pathways in spinocerebellar ataxia type 3.

At least seven dominantly inherited spinocerebellar ataxias (SCA) are caused by expansions of polyglutamine (polyQ)-encoding CAG repeat. The misfolded and aggregated polyQ-expanded proteins increase reactive oxygen species (ROS), cellular toxicity, and neuroinflammation in the disease pathogenesis. In this study, we evaluated the anti-inflammatory potentials of coumarin derivatives LM-021, LMDS-1, LMDS-2, and pharmacological chaperone tafamidis using mouse BV-2 microglia and SCA3 ataxin-3 (ATXN3)/Q75-GFP SH-SY5Y cells. The four tested compounds displayed anti-inflammatory activity by suppressing nitric oxide (NO), interleukin (IL)-1ß, IL-6, and tumor necrosis factor (TNF)-α production, and CD68 antigen (CD68) and histocompatibility-2 (MHCII) expression in lipopolysaccharides (LPS)/interferon (IFN)-γ-stimulated BV-2 microglia. In retinoic acid-differentiated ATXN3/Q75-GFP-expressing SH-SY5Y cells inflamed with LPS/IFN-γ-primed BV-2 conditioned medium, treatment with test compounds mitigated the increased caspase 1 activity and lactate dehydrogenase release, reduced ROS and ATXN3/Q75 aggregation, and promoted neurite outgrowth. Examination of IL-1ß and IL-6-mediated signaling pathways revealed that LM-021, LMDS-1, LMDS-2, and tafamidis decreased NLR family pyrin domain containing 1 (NLRP1), c-Jun N-terminal kinase/c-Jun proto-oncogene (JNK/JUN), inhibitor of kappa B (IκBα)/P65, mitogen-activated protein kinase 14/signal transducer and activator of transcription 1 (P38/STAT1), and/or Janus kinase 2/signal transducer and activator of transcription 3 (JAK2/STAT3) signaling. The study results suggest the potential of LM-021, LMDS-1, LMDS-2, and tafamidis in treating SCA3 and probable other polyQ diseases.

A Two-Stage Attention-Based Hierarchical Transformer for Turbofan Engine Remaining Useful Life Prediction.

The accurate estimation of the remaining useful life (RUL) for aircraft engines is essential for ensuring safety and uninterrupted operations in the aviation industry. Numerous investigations have leveraged the success of the attention-based Transformer architecture in sequence modeling tasks, particularly in its application to RUL prediction. These studies primarily focus on utilizing onboard sensor readings as input predictors. While various Transformer-based approaches have demonstrated improvement in RUL predictions, their exclusive focus on temporal attention within multivariate time series sensor readings, without considering sensor-wise attention, raises concerns about potential inaccuracies in RUL predictions. To address this concern, our paper proposes a novel solution in the form of a two-stage attention-based hierarchical Transformer (STAR) framework. This approach incorporates a two-stage attention mechanism, systematically addressing both temporal and sensor-wise attentions. Furthermore, we enhance the STAR RUL prediction framework by integrating hierarchical encoder-decoder structures to capture valuable information across different time scales. By conducting extensive numerical experiments with the CMAPSS datasets, we demonstrate that our proposed STAR framework significantly outperforms the current state-of-the-art models for RUL prediction.

Epidemiology of spinal cord injury and spinal cord injury-induced urinary tract stones in Taiwan: A 2005-2015 population-based cohort study.

CONTEXT: Patients with spinal cord injury (SCI) can develop urinary tract stones (UTSs) up to years after the injury, which is especially common in the first few months. However, relevant epidemiological studies and up-to-date epidemiological data for SCI in Taiwan are lacking. PURPOSE: To estimate SCI and SCI-induced UTS incidence and trauma severity, neurological deficits, and injury site in patients with SCI-induced UTSs in Taiwan. DESIGN: Retrospective cohort study.Patient sample: Taiwan National Health Insurance Research Database (NHIRD) data and death data from the Department of Health and Welfare Data Science Center (HWDC) collected over 2005-2015 from 13,977 patients with SCI aged >18 years. OUTCOME MEASURES: Cumulative incidence (CI), incidence density (ID), relative ratios (RRs), odds ratios (ORs), and hazard ratios (HRs) were measured. METHODS: By using Cox regression, we assessed UTS risk in patients with SCI. RESULTS: Although standardized SCI incidence demonstrated a decreasing trend annually, the average annual incidence remained at 60.4 per million. Most (65.7%) of the included patients were men. SCI incidence was 1.98 times higher in men than in women. The most common injury site was the cervical spine (63.8%); the incidence at this site was 2.83 times higher in men than in women. Most (76.1%) of the patients had traumatic SCI (TSCI), and the standardized incidence of TSCI and non-TSCI was 45.9 and 14.4 per million, respectively. 46.1% of the patients had severe SCI (RISS ≥ 16). Over the 11-year follow-up period, UTSs occurred in 10.4% of the patients, with a standardized incidence of 2.39 per 100 person-years, and UTS risk was 1.56 times higher in men than in women. Age of 45-65 years, SCIs at multiple sites, and neurological deficits (e.g. paraplegia) were noted to be UTS risk factors. Finally, UTS onset mainly occurred in the first year after SCI. CONCLUSION: The risk of UTS among patients with SCI is influenced by age, sex, injury site, and paraplegia but not by paralysis resulting from other neurological deficits. Even though SCI incidence is declining annually, severe SCI remains a significant issue. Therefore, continuing to reduce SCI incidence and strengthening urinary tract management in patients with SCI are essential for reducing UTS occurrence and their impact on health.

PD-L1-positive circulating endothelial progenitor cells associated with immune response to PD-1 blockade in patients with head and neck squamous cell carcinoma.

A number of the inhibitors against programmed death protein 1 (PD-1) have been approved to treat recurrent or metastatic squamous cell carcinoma of head and neck (HNSCC). The interaction between PD-1 and its ligand (PD-L1) serves as an immune checkpoint that governs cytotoxic immune effectors against tumors. Numerous clinical trials of PD-1/PD-L1 inhibitors have so far been discordant about having sufficient PD-L1 expression in the tumor as a prerequisite for a successful anti-PD-1 treatment. On the other hand, vascular endothelial cells modulate immune activities through PD-L1 expression, and thus it is possible that the expressions of circulating endothelial cells (CECs) and circulating endothelial progenitor cells (CPCs) could affect antitumor immunity as well as neoangiogenesis. Here we investigated the potential involvement of PD-L1+ CECs and PD-L1+ CPCs in PD-1 blockade treatments for HNSCC patients. We measured CD8+ T cells, CECs, and CPCs in the peripheral blood of the HNSCC patients treated by anti-PD-1 therapies. We found that their PD-L1+ CPC expression before anti-PD1 therapies was strongly correlated with treatment responses and overall survival. Moreover, if the first infusion of PD-1 inhibitors reduced ≥ 50% PD-L1+ CPCs, a significantly better outcome could be predicted. In these patients as well as in an animal model of oral cancer, Pd-l1+ CPC expression was associated with limited CD8+ T-cell infiltration into the tumors, and anti-PD-1 treatments also targeted Pd-l1+ CPCs and increased CD8+ T-cell infiltration. Our results highlight PD-L1+ CPC as a potential regulator in the anti-PD-1 treatments for HNSCC.

Ten-year follow-up investigation of stroke risk in systemic lupus erythematosus.

BACKGROUND AND PURPOSE: To analyse the long-term risk of ischaemic stroke and the clinical effects of antithrombotics on the risk of haemorrhagic stroke in patients with systemic lupus erythematosus (SLE). METHODS: A retrospective cohort study was conducted using a population-based database taken from Taiwan National Health Insurance Research Database. Patients with SLE between 2000 and 2008 were registered and matched with two controls by the index date, age, gender and Charlson Comorbidity Index (CCI). These subjects were followed until either stroke event or 31 December 2013. Adjusted HRs (aHRs) for strokes were estimated with Cox regression models, and the cumulative incidence of ischaemic stroke was analysed by log-rank test and Kaplan-Meier survival analysis. RESULTS: In total, 8310 patients with SLE and 16 620 patients without SLE were included. In general, patients with SLE had higher rates of ischaemic stroke (5.4% vs 3.3%) and haemorrhagic stroke (1.5% vs 0.6%) than in controls. In multivariate analysis adjusted to age, gender, CCI, urbanisation level and antithrombotics uses, aHRs of all strokes, ischaemic stroke and haemorrhagic stroke were 1.73 (95% CI: 1.54 to 1.94), 1.65 (95% CI: 1.45 to 1.87) and 2.24 (95% CI: 1.71 to 2.95), respectively, in patients with SLE. Patients with SLE were significantly more likely to suffer ischaemic stroke than patients without SLE, even 10 years after SLE diagnosis (6.12% vs 3.50%, p<0.001). Antiplatelet use increased the risk of haemorrhagic stroke in SLE group (aHR=1.74, 95% CI: 1.18 to 2.57). CONCLUSIONS: Patients with SLE are at greater risk of developing ischaemic stroke that lasts for 10 years. Antiplatelets should be carefully administered to prevent cardiovascular events in patients with SLE due to the risk of haemorrhagic stroke.

Advanced hepatocellular carcinoma with major portal vein invasion: Therapeutic outcomes of hepatic arterial infusion chemotherapy vs concurrent radiotherapy.

BACKGROUND: Hepatocellular carcinoma (HCC) with major portal vein invasion (MPVI) presents very poor outcomes. Hepatic artery infusion chemotherapy (HAIC) and radiation therapy (RT) have both been found to be effective for advanced HCC. In this retrospective study, we compared the therapeutic outcomes of our "new" HAIC regimen with and without concurrent RT, before and after propensity score matching (PSM) in treating HCC patients with MPVI. METHODS: One hundred forty patients with MPVI received HAIC alone and 35 patients underwent concurrent HAIC and RT during a 16-year period. The left subclavian artery was adopted as the entry site for a temporary catheter placement for a 5-day chemoinfusion. The Modified Response Evaluation Criteria in Solid Tumors (mRECIST) was adopted to assess the objective response rate (ORR). The Kaplan-Meier curve was used to calculate progression-free survival (PFS) and overall survival (OS) between the two groups. Univariate and multivariate analyses by Cox regression model were used to assess hazard ratios. RESULTS: Of the 140 patients with Child-Pugh A liver function, the median OS was 17.0 months. In the initial cohort, higher ORR and PFS were found in the concurrent RT group than in the HAIC alone group (80% vs 66.4% and 9 vs 8 months, respectively) but shorter OS (10.5 vs 14.5 months, p = 0.039) was observed. After PSM, the OS was 10 and 15 months ( p = 0.012), respectively. Multivariable Cox regression analysis revealed that the significant factors for adjusting hazard ratios for OS were Child-Pugh classification, alpha fetal protein (AFP) level, and hepatic vein invasion. CONCLUSION: HAIC is an effective treatment for advanced HCC patients with MPVI. Concurrent HAIC and full-dose RT were associated with worse clinical outcomes.

Characteristics of acute ischemic stroke in patients with Nephrotic syndrome.

The incidence of ischemic stroke (IS) is higher in nephrotic syndrome (NS) patients compared to general population. However, there is limited information on the specific characteristics to stroke patients with NS. In this study, we aimed to examine the clinical manifestations of acute IS in a large group of NS patients, comparing to those without NS. We conducted a retrospective cohort study to compare the clinical presentations of acute IS in patients with and without NS. This study was a multi-institutional study and used data from Chang Gung Research Database of Taiwan from 1 January 2001, to 31 December 2017. A total of 233 IS patients with NS and 1358 IS patients without NS were enrolled. The median age of participants was 68 (range: 59-79) years. The risk of dependent functional status (modified Rankin Scale score≧3) after IS was higher in NS patients compared to those without NS (Odd ratio (OR) 4.02, 95% confidence interval (CI) 2.39 to 6.76, p < 0.001), particularly in stroke subtypes as small-artery occlusion (OR 8.02, 95% CI 3.94 to 16.32, p < 0.001), and stroke of undetermined etiology (OR 2.47, CI 1.06 to 5.76, p = 037). The risks of mortality or stroke recurrence within 30 days were similar between the two groups for all stroke subtypes. In conclusion, NS was associated with a higher risk of functional dependence following IS. Intensive treatment and rehabilitation should be considered for IS patients with NS.

Cold Atmospheric Plasma Jet Irradiation Decreases the Survival and the Expression of Oncogenic miRNAs of Oral Carcinoma Cells.

Despite recent advancements, therapies against advanced oral squamous cell carcinoma (OSCC) remain ineffective, resulting in unsatisfactory therapeutic outcomes. Cold atmospheric plasma (CAP) offers a promising approach in the treatment of malignant neoplasms. Although the effects of CAP in abrogating OSCC have been explored, the exact mechanisms driving CAP-induced cancer cell death and the changes in microRNA (miRNA) expression are not fully understood. We fabricated and calibrated an argon-CAP device to explore the effects of CAP irradiation on the growth and expression of oncogenic miRNAs in OSCC. The analysis revealed that, in OSCC cell lines following CAP irradiation, there was a significant reduction in viability; a downregulation of miR-21, miR-31, miR-134, miR-146a, and miR-211 expression; and an inactivation of the v-akt murine thymoma viral oncogene homolog (AKT) and extracellular signal-regulated kinase (ERK) signals. Pretreatment with blockers of apoptosis, autophagy, and ferroptosis synergistically reduced CAP-induced cell death, indicating a combined induction of variable death pathways via CAP. Combined treatments using death inhibitors and miRNA mimics, alongside the activation of AKT and ERK following the exogenous expression, counteracted the cell mortality associated with CAP. The CAP-induced downregulation of miR-21, miR-31, miR-187, and miR-211 expression was rescued through survival signaling. Additionally, CAP irradiation notably inhibited the growth of SAS OSCC cell xenografts on nude mice. The reduced expression of oncogenic miRNAs in vivo aligned with in vitro findings. In conclusion, our study provides new lines of evidence demonstrating that CAP irradiation diminishes OSCC cell viability by abrogating survival signals and oncogenic miRNA expression.

Dental pulp cells cocultured with macrophages aggravate the inflammatory conditions stimulated by LPS.

BACKGROUND: Pulp inflammation is complex interactions between different types of cells and cytokines. To mimic the interactions of different types of cells in inflamed dental pulp tissues, dental pulp cells (DPCs) were cocultured with different ratios of macrophages (THP-1) or LPS treatment. METHODS: DPCs were cocultured with various ratios of THP-1, then photographed cell morphology and determined cell viability by MTT assay at preset times. Total RNA was also extracted to measure the inflammation marker-IL-6 and IL-8 expressions by RT-Q-PCR. The DPCs and THP-1 were treated with 0.01 - 1µg/ml lipopolysaccharide (LPS) and extract RNA at preset times, and detected IL-6 and IL-8 expression. DPCs were cocultured with various ratios of THP-1 with 0.1 µg/mL LPS, and detected IL-6 and IL-8 expression after 24 and 48 h. The data were analyzed by unpaired t-test or Mann-Whitney test. Differences were considered statistically significant when p < 0.05. RESULTS: THP-1 and DPCs coculture models did not suppress the viability of DPCs and THP-1. Cocultured with various ratios of THP-1 could increase IL-6 and IL-8 expressions of DPCs (p = 0.0056 - p < 0.0001). The expressions of IL-6 and IL-8 were stronger in higher ratio groups (p = 0.0062 - p < 0.0001). LPS treatment also induced IL-6 and IL-8 expressions of DPCs and THP-1 (p = 0.0179 - p < 0.0001 and p = 0.0189 - p < 0.0001, separately). Under the presence of 0.1 µg/mL LPS, DPCs cocultured with THP-1 for 24 h also enhanced IL-6 and IL-8 expression (p = 0.0022). After cocultured with a higher ratio of THP-1 for 48 h, IL-6 and IL-8 expressions were even stronger in the presence of LPS (p = 0.0260). CONCLUSIONS: Coculturing dental pulp cells and macrophages under LPS treatment aggravate the inflammatory process. The responses of our models were more severe than traditional inflamed dental models and better represented what happened in the real dental pulp. Utilizing our models to explore the repair and regeneration in endodontics will be future goals.