Development of an equation to predict delta bilirubin levels using machine learning.

OBJECTIVE: Delta bilirubin (albumin-covalently bound bilirubin) may provide important clinical utility in identifying impaired hepatic excretion of conjugated bilirubin, but it cannot be measured in real-time for diagnostic purposes in clinical laboratories. METHODS: A total of 210 samples were collected, and their delta bilirubin levels were measured four times using high-performance liquid chromatography. Data collected included age, sex, diagnosis code, delta bilirubin, total bilirubin, direct bilirubin, total protein, albumin, globulin, aspartate aminotransferase, alanine transaminase, alkaline phosphatase, gamma-glutamyl transferase, lactate dehydrogenase, hemoglobin, serum hemolysis value, hemolysis index, icterus value (Iv), icterus index (Ii), lipemia value (Lv), and lipemia index. To conduct feature selection and identify the optimal combination of variables, linear regression machine learning was performed 1,000 times. RESULTS: The selected variables were total bilirubin, direct bilirubin, total protein, albumin, hemoglobin, Iv, Ii, and Lv. The best predictive performance for high delta bilirubin concentrations was achieved with the combination of albumin-direct bilirubin-hemoglobin-Iv-Lv. The final equation composed of these variables was as follows: delta bilirubin = 0.35 × Iv + 0.05 × Lv - 0.23 × direct bilirubin - 0.05 × hemoglobin - 0.04 × albumin + 0.10. CONCLUSION: The equation established in this study is practical and can be easily applied in real-time in clinical laboratories.

Impact of the COVID-19 pandemic on telogen effluvium: a nationwide multicentre interrupted time series study.

BACKGROUND: There is ongoing debate regarding the association between telogen effluvium (TE) and COVID-19, as well as COVID-19 vaccines. OBJECTIVES: To investigate the impact of the COVID-19 pandemic and vaccination on the development of TE among patients visiting dermatology clinics in South Korea. METHODS: Between 2017 and 2022, data regarding patients with TE and other types of hair loss were collected from 22 hospitals in South Korea. An interrupted time series analysis was conducted, dividing the time into periods before and after the COVID-19 pandemic, as well as before and after the COVID-19 vaccination. RESULTS: There was a significant slope change in the percentage of cases of TE during the postpandemic period (slope change 0.011, 95% confidence interval 0.005-0.017, P < 0.001), but no significant changes were observed after vaccination. The percentage of patients with other types of hair loss was not associated with COVID-19 or vaccination. The retrospective nature of the study may have limited the ability to establish causation. CONCLUSIONS: This multicentre study provides insights into the epidemiology of TE, showing a significant increase in cases of TE following the COVID-19 pandemic. However, there was no association between the occurrence of TE and COVID-19 vaccines.

Establishing Medical Intelligence - Leveraging FHIR to Improve Clinical Management: a retrospective cohort and clinical implementation study.

BACKGROUND: FHIR (Fast Healthcare Interoperability Resources) has been proposed to enable health data interoperability. So far, its applicability has been demonstrated for selected research projects with limited data. OBJECTIVE: Here, we designed and implemented a conceptual medical intelligence framework to leverage real-world care data for clinical decision-making. METHODS: A Python package for the utilization of multimodal FHIR data (FHIRPACK) was developed and pioneered in five real-world clinical use cases, i.e., myocardial infarction (MI), stroke, diabetes, sepsis, and prostate cancer (PC). Patients were identified based on ICD-10 codes, and outcomes were derived from laboratory tests, prescriptions, procedures, and diagnostic reports. Results were provided as browser-based dashboards. RESULTS: For 2022, 1,302,988 patient encounters were analyzed. MI: In 72.7% of cases (N=261) medication regimens fulfilled guideline recommendations. Stroke: Out of 1,277 patients, 165 patients received thrombolysis and 108 thrombectomy. Diabetes: In 443,866 serum glucose and 16,180 HbA1c measurements from 35,494 unique patients, the prevalence of dysglycemic findings was 39% (N=13,887). Among those with dysglycemia, diagnosis was coded in 44.2% (N=6,138) of the patients. Sepsis: In 1,803 patients, Staphylococcus epidermidis was the primarily isolated pathogen (N=773, 28.9%) and piperacillin/tazobactam was the primarily prescribed antibiotic (N=593, 37.2%). PC: Three out of 54 patients who received radical prostatectomy were identified as cases with PSA persistence or biochemical recurrence. CONCLUSIONS: Leveraging FHIR data through large-scale analytics can enhance healthcare quality and improve patient outcomes across five clinical specialties. We identified i) sepsis patients requiring less broad antibiotic therapy, ii) patients with myocardial infarction who could benefit from statin and antiplatelet therapy, iii) stroke patients with longer than recommended times to intervention, iv) patients with hyperglycemia who could benefit from specialist referral and v) PC patients with early increases in cancer markers.

Differentiating Left Atrial Pressure Responses in Paroxysmal and Persistent Atrial Fibrillation: Implications for Diagnosing Heart Failure With Preserved Ejection Fraction and Managing Atrial Fibrillation.

BACKGROUND: Increased left atrial pressure (LAP) contributes to dyspnea and heart failure with preserved ejection fraction in patients with atrial fibrillation (AF). The purpose of this study was to investigate the differences in baseline LAP and LAP response to rapid pacing between paroxysmal and persistent AF. METHODS AND RESULTS: This observational study prospectively enrolled 1369 participants who underwent AF catheter ablation, excluding those with reduced left ventricular ejection fraction. H2FPEF score was calculated by echocardiography and baseline characteristics. Patients underwent LAP measurements during AF, sinus rhythm, and heart rates of 90, 100, 110, and 120 beats per minute (bpm), induced by right atrial pacing and isoproterenol. The baseline LAP-peak in the persistent AF group consistently exceeded that in the paroxysmal AF (PAF) group across each H2FPEF score subgroup (all P<0.05). LAP-peak increased with pacing (19.5 to 22.5 mm Hg) but decreased with isoproterenol (20.4 to 18.4 mm Hg). Under pacing, patients with PAF exhibited a significantly lower LAP-peak (90 bpm) than those with persistent AF (17.7±8.2 versus 21.1±9.3 mm Hg, P<0.001). However, there was no difference in LAP-peak (120 bpm) between the 2 groups (22.1±8.1 versus 22.9±8.4 mm Hg, P=0.056) because the LAP-peak significantly increased with heart rate in the group with PAF. CONCLUSIONS: Patients with PAF exhibited lower baseline LAP with greater increases during rapid pacing compared with individuals with persistent AF, indicating a need to revise the H2FPEF score for distinguishing PAF from persistent AF and emphasizing the importance of rate and rhythm control in PAF for symptom control. REGISTRATION: URL: https://www.clinicaltrials.gov; Unique Identifier: NCT02138695.

IFN-ß Overexpressing Adipose-Derived Mesenchymal Stem Cells Mitigate Alcohol-Induced Liver Damage and Gut Permeability.

Alcoholic liver disease (ALD) is a form of hepatic inflammation. ALD is mediated by gut leakiness. This study evaluates the anti-inflammatory effects of ASCs overexpressing interferon-beta (ASC-IFN-ß) on binge alcohol-induced liver injury and intestinal permeability. In vitro, ASCs were transfected with a non-viral vector carrying the human IFN-ß gene, which promoted hepatocyte growth factor (HGF) secretion in the cells. To assess the potential effects of ASC-IFN-ß, C57BL/6 mice were treated with three oral doses of binge alcohol and were administered intraperitoneal injections of ASC-IFN-ß. Mice treated with binge alcohol and administered ASC-IFN-ß showed reduced liver injury and inflammation compared to those administered a control ASC. Analysis of intestinal tissue from ethanol-treated mice administered ASC-IFN-ß also indicated decreased inflammation. Additionally, fecal albumin, blood endotoxin, and bacterial colony levels were reduced, indicating less gut leakiness in the binge alcohol-exposed mice. Treatment with HGF, but not IFN-ß or TRAIL, mitigated the ethanol-induced down-regulation of cell death and permeability in Caco-2 cells. These results demonstrate that ASCs transfected with a non-viral vector to induce IFN-ß overexpression have protective effects against binge alcohol-mediated liver injury and gut leakiness via HGF.

AI-derived body composition parameters as prognostic factors in patients with HCC undergoing TACE in a multicenter study.

Background & Aims: Body composition assessment (BCA) parameters have recently been identified as relevant prognostic factors for patients with hepatocellular carcinoma (HCC). Herein, we aimed to investigate the role of BCA parameters for prognosis prediction in patients with HCC undergoing transarterial chemoembolization (TACE). Methods: This retrospective multicenter study included a total of 754 treatment-naïve patients with HCC who underwent TACE at six tertiary care centers between 2010-2020. Fully automated artificial intelligence-based quantitative 3D volumetry of abdominal cavity tissue composition was performed to assess skeletal muscle volume (SM), total adipose tissue (TAT), intra- and intermuscular adipose tissue, visceral adipose tissue, and subcutaneous adipose tissue (SAT) on pre-intervention computed tomography scans. BCA parameters were normalized to the slice number of the abdominal cavity. We assessed the influence of BCA parameters on median overall survival and performed multivariate analysis including established estimates of survival. Results: Univariate survival analysis revealed that impaired median overall survival was predicted by low SM (p <0.001), high TAT volume (p = 0.013), and high SAT volume (p = 0.006). In multivariate survival analysis, SM remained an independent prognostic factor (p = 0.039), while TAT and SAT volumes no longer showed predictive ability. This predictive role of SM was confirmed in a subgroup analysis of patients with BCLC stage B. Conclusions: SM is an independent prognostic factor for survival prediction. Thus, the integration of SM into novel scoring systems could potentially improve survival prediction and clinical decision-making. Fully automated approaches are needed to foster the implementation of this imaging biomarker into daily routine. Impact and implications: Body composition assessment parameters, especially skeletal muscle volume, have been identified as relevant prognostic factors for many diseases and treatments. In this study, skeletal muscle volume has been identified as an independent prognostic factor for patients with hepatocellular carcinoma undergoing transarterial chemoembolization. Therefore, skeletal muscle volume as a metaparameter could play a role as an opportunistic biomarker in holistic patient assessment and be integrated into decision support systems. Workflow integration with artificial intelligence is essential for automated, quantitative body composition assessment, enabling broad availability in multidisciplinary case discussions.

Effects of antiarrhythmic drug responsiveness and diagnosis-to-ablation time on outcomes after catheter ablation for persistent atrial fibrillation.

Background: The impact of delaying atrial fibrillation catheter ablation (AFCA) for antiarrhythmic drug (AAD) management on the disease course remains unclear. This study investigated AFCA rhythm outcomes based on the diagnosis-to-ablation time (DAT) and AAD responsiveness in participants with persistent AF (PeAF). Methods: We included data from 1038 AAD-resistant PeAF participants, all of whom had a clear time point for AF diagnosis, especially PeAF at diagnosis time, and had undergone an AFCA for the first time. Participants who experienced recurrences of paroxysmal type on AAD therapy were analyzed as a cohort of AAD-partial responders; those maintaining PeAF on AAD were AAD-non-responders. We determined the DAT cutoff for best discriminating long-term rhythm outcomes using a maximum log-likelihood estimation method based on the Cox proportional hazard regression model. Results: Of the participants (79.8% male; median age 61), 806 (77.6%) were AAD-non-responders. AAD-non-responders had a higher body mass index and a larger left atrial diameter than AAD-partial-responders. They also had a higher incidence of AF recurrence after AFCA (adjusted hazard ratio 1.75, 95% confidence interval 1.33-2.30; log-rank p < .001) compared to AAD-partial-responders. The maximum log-likelihood estimation showed bimodal cutoffs at 22 and 40 months. The optimal DAT cutoff rhythm outcome was 22 months, which discriminated better in the AAD-partial-responders than in the AAD-non-responders. Conclusions: Both DAT and AAD responsiveness influenced AFCA rhythm outcomes. Delaying AFCA to a DAT of longer than 22 months was inadvisable, particularly in the participants in whom PeAF was changed to paroxysmal AF during AAD therapy.

Preventive machine learning models incorporating health checkup data and hair mineral analysis for low bone mass identification.

Machine learning (ML) models have been increasingly employed to predict osteoporosis. However, the incorporation of hair minerals into ML models remains unexplored. This study aimed to develop ML models for predicting low bone mass (LBM) using health checkup data and hair mineral analysis. A total of 1206 postmenopausal women and 820 men aged 50 years or older at a health promotion center were included in this study. LBM was defined as a T-score below - 1 at the lumbar, femur neck, or total hip area. The proportion of individuals with LBM was 59.4% (n = 1205). The features used in the models comprised 50 health checkup items and 22 hair minerals. The ML algorithms employed were Extreme Gradient Boosting (XGB), Random Forest (RF), Gradient Boosting (GB), and Adaptive Boosting (AdaBoost). The subjects were divided into training and test datasets with an 80:20 ratio. The area under the receiver operating characteristic curve (AUROC), accuracy, sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV) and an F1 score were evaluated to measure the performances of the models. Through 50 repetitions, the mean (standard deviation) AUROC for LBM was 0.744 (± 0.021) for XGB, the highest among the models, followed by 0.737 (± 0.023) for AdaBoost, and 0.733 (± 0.023) for GB, and 0.732 (± 0.021) for RF. The XGB model had an accuracy of 68.7%, sensitivity of 80.7%, specificity of 51.1%, PPV of 70.9%, NPV of 64.3%, and an F1 score of 0.754. However, these performance metrics did not demonstrate notable differences among the models. The XGB model identified sulfur, sodium, mercury, copper, magnesium, arsenic, and phosphate as crucial hair mineral features. The study findings emphasize the significance of employing ML algorithms for predicting LBM. Integrating health checkup data and hair mineral analysis into these models may provide valuable insights into identifying individuals at risk of LBM.

Transcriptomic analysis for the gamma-ray-induced sweetpotato mutants with altered stem growth pattern.

Introduction: Sweetpotato faces breeding challenges due to physiological and genomic issues. Gamma radiation is a novel approach for inducing genetic variation in crops. We analyzed the transcriptomic changes in gamma ray-induced sweetpotato mutants with altered stem development compared with those in the wild-type 'Tongchaeru' cultivar. Methods: RNA sequencing analyses were performed to identify changes in the expression of genes related to stem development. Results: Transcriptomic analysis identified 8,931 upregulated and 6,901 downregulated genes, including the upregulation of the auxin-responsive SMALL AUXIN UP RNA (SAUR) and three PHYTOCHROME INTERACTING FACTOR 4 (PIF4) genes. PIF4 is crucial for regulating the expression of early auxin-responsive SAUR genes and stem growth in Arabidopsis thaliana. In the mutant, several genes related to stem elongation, including PIF4 and those involved in various signaling pathways such as auxin and gibberellin, were upregulated. Discussion: Our results suggest that gamma ray-induced mutations influence auxin-dependent stem development by modulating a complex regulatory network involving the expression of PIF4 and SAUR genes, and other signaling pathways such as gibberellin and ethylene signaling genes. This study enhances our understanding of the regulatory mechanisms underlying stem growth in sweetpotato, providing valuable insights for genomics-assisted breeding efforts.

Fundamental Limits of the Spatial Control of Heterogeneous Nucleation on Biphilic Surfaces.

Condensation of water vapor on nonwetting surfaces, termed dropwise condensation, leads to rapid droplet removal and significantly improves heat transfer compared to wetting surfaces. However, the spatial distribution of heterogeneous nucleation sites during dropwise condensation is random. Furthermore, the low surface energy of the nonwetting substrate reduces the nucleation rate as predicted by classical nucleation theory. To achieve higher nucleation rates, biphilic surfaces having low nucleation energy barriers that rely on spatial heterogeneity of surface chemistry have been developed. Here, we use a robust method to create biphilic surfaces on flat and micropillar samples having various dimensions (pillar lengths: 10-15 µm, pillar heights: 0-15 µm) by utilizing lift-off microfabrication. Our fabrication approach leads to hydrophilic pillar tops and hydrophobic pillar sides and surrounding basal areas. To study water vapor condensation on the biphilic surfaces, we utilized optical microscopy in a controlled temperature and humidity environment. Interestingly, our studies show that while the majority of nucleation (≈100%) occurred only on the hydrophilic areas (pillar tops) for small pillar center-to-center spacing (pitch), the spatial control of heterogeneous nucleation broke down when the pitch increased. For larger pitches, we observed the nucleation of water droplets on the hydrophobic base in conjunction with hydrophilic pillar tops. Using theoretical models of vapor diffusion coupled with heat transfer and three-dimensional (3D) numerical simulations, we show that nucleation initiation on hydrophilic pillar tops leads to the formation of dry zones, preventing nucleation on hydrophobic regions. However, with increasing pitch, part of the hydrophobic region no longer feels the presence of the vapor depletion zone, resulting in subsequent nucleation at defect sites on the hydrophobic regions at the base. Our study offers insights into the fundamental limitations of biphilic condensation and offers avenues for their further improvement for applications such as boiling, icing, evaporation, and condensation.

Lower respiratory tract microbiota in patients with clinically suspected nontuberculous mycobacterial pulmonary disease according to the presence of gastroesophageal reflux.

Although gastroesophageal reflux has been recognized as one of the risk factors of nontuberculous mycobacterial pulmonary disease (NTM-PD) progression, the effect of reflux on the lower respiratory tract microbiota has not been studied in detail. We investigated the composition of the lower respiratory tract microbiota in patients with clinically suspected NTM-PD, comparing them based on the presence of reflux. Forty-seven patients suspected of having NTM-PD were enrolled and assigned according to presence of reflux (n = 22) and non- reflux (n = 25). We performed a pepsin ELISA assay to identify the presence of reflux and 16S ribosomal RNA gene amplicon sequencing to evaluate the microbiota in bronchoalveolar lavage fluid. There were no significant differences in the diversity or composition of the lower respiratory microbiota between the NTM-PD and non-NTM-PD groups. Bacterial richness was observed in the non-reflux group than in the reflux group [P = 0.03] and a cluster in the reflux group was observed. The reflux group showed a predominance for Pseudomonas aeruginosa or Staphylococcus aureus among the NTM-PD group and for P. aeruginosa, Haemophilus influenzae, Klebsiella pneumoniae, or Eikenella species among the non-NTM-PD group. The non-reflux groups presented diverse patterns. A linear discriminant analysis and volcano plot demonstrated that P. aeruginosa, H. haemolyticus, Selenomonas artemidis, and Dolosigranulum pigrum were specifically associated with the NTM-PD reflux group, while P. aeruginosa was specifically associated with the non-NTM-PD reflux group. These observations confirm that the lower respiratory microbiota is consistently altered by reflux but not in NTM-PD.

Pituitary tumor­transforming gene 1 regulates the senescence and apoptosis of oral squamous cell carcinoma in a p21­dependent DNA damage response manner.

Pituitary tumor­transforming gene 1 (PTTG1), also known as securin, is a proto­oncogene involved in the development of various cancers by promoting cell proliferation and mobility. However, its underlying biological mechanisms in oral squamous cell carcinoma (OSCC) progression remain unclear. in the present study, it was sought to elucidate the role of PTTG1 as an oncogene in OSCC progression and was attempted to unravel the underlying mechanism and impact of PTTG1 expression on cell cycle, cell death, and cellular senescence. The effect of double strand break on PTTG1 expression was investigated in OSCC growth. To identify the role of PTTG1 in OSCC growth, the cell viability and senescence was analyzed by EdU and senescence­associated beta­galactosidase (SA­ß­gal) assay, respectively. To verify the DNA damage­induced senescence of PTTG1, the chromosomal damage in OSCC was analyzed in vitro. Finally, the effect of PTTG1 on tumor growth and gene expression related to cell viability and DNA damaged­induced senescence was investigated in vivo. PTTG1 expression was compared between OSCC and healthy patient samples (n=32) using reverse transcription­quantitative PCR and immunohistochemistry; and it was found that PTTG1 expression was upregulated in OSCC. Small interfering RNA­mediated knockdown of PTTG1 in two OSCC cell lines revealed that PTTG1 downregulation significantly inhibited cell proliferation and arrested the cell cycle pathway as evidenced by changes in checkpoint genes (such as cyclin D1, E and B1). PTTG1 knockdown also increased apoptosis, as evidenced by the upregulation of apoptotic genes [such as cleaved (c­) Caspase­7 and c­poly (ADP­ribose) polymerase]. Moreover, PTTG1 downregulation promoted cellular senescence, as shown by western blotting and SA­ß­gal staining. Finally, senescence­induced DNA damage was observed in OSCC cells, which accelerates genomic instability, through chromosomal damage analysis. Taken together, the present findings suggested that PTTG1 acts as a proto­oncogene; regulates cell proliferation, cell cycle, cellular senescence and DNA damage in OSCC; and may serve as a novel diagnostic biomarker and potential therapeutic target for OSCC.

Post-extraction bleeding in patients on direct oral anticoagulants.

Objectives: This study aimed to evaluate the association between use of direct oral anticoagulants (DOACs) and post-extraction bleeding and to quantify bleeding risk in patients receiving DOACs. Materials and Methods: The study included 293 patients who were taking DOACs and underwent tooth extraction (414 teeth). The patients were divided into those who had the extraction while taking DOACs and those who discontinued DOACs before the extraction. Bleeding complications were recorded and compared between the patient groups and types of DOACs. Results: Of the 293 patients, 12 patients (6.9%) had post-extraction bleeding. Post-extraction bleeding occurred in 12 of the 414 tooth extraction sites. Among the 246 patients who underwent dental extraction while continuing DOAC therapy, 12 patients (8.5%) had post-extraction bleeding. Among the 47 patients who underwent dental extraction after discontinuing the administration of DOACs, none reported post-extraction bleeding. There was no significant difference in the number of patients with post-extraction bleeding between the two groups (P=0.122). Conclusion: Continuing DOAC therapy during dental extraction does not increase post-extraction bleeding tendency. These results are consistent with those of previous studies.

The RING-type E3 ligase, TaFRFP, regulates flowering by controlling a salicylic acid-mediated floral promotion.

The initiation of transition to flowering is carefully managed by endogenous and environmental cues, which is critical for flowering plant reproductive success. Here, we found that wheat RING-type E3 ligase TaFRFP was highly expressed from the double ridge to degeneration stage (WS2.5-WS9). TaFRFP is localized in the nucleus and has E3 ligase activity in vitro. TaFRFP overexpression in Arabidopsis resulted in an early flowering phenotype, but to a lesser extent, under short-day conditions. Under the SA-treated condition, overexpression of TaFRFP shows higher root growth and has more accumulation of SA contents. A proteomic comparison revealed that the amount of FRL4A protein, a FRIGIDA LIKE 4 A, was considerably lower in SA-treated TaFRFP seedlings compared to normal condition. We further found that TaFRFP directly interacts with FRL4A in the nucleus and recruits it to the FLC locus in Arabidopsis. Moreover, an ubiquitination assay showed that TaFRPF physically interact and ubiquitinates TaFRL as a substrate. Our findings support the concept that the TaFRFP E3 ligase works as a positive regulator, and that the ubiquitination of its substrate proteins plays a significant role in controlling flowering time via an SA-dependent pathway.

Dual imaging technique for a real-time inspection system of foreign object detection in fresh-cut vegetables.

Fresh-cut vegetables are a food product susceptible to contamination by foreign materials (FMs). To detect a range of potential FMs in fresh-cut vegetables, a dual imaging technique (fluorescence and color imaging) with a simple and effective image processing algorithm in a user-friendly software interface was developed for a real-time inspection system. The inspection system consisted of feeding and sensing units, including two cameras positioned in parallel, illuminations (white LED and UV light), and a conveyor unit. A camera equipped with a long-pass filter was used to collect fluorescence images. Another camera collected color images of fresh-cut vegetables and FMs. The feeding unit fed FMs mixed with fresh-cut vegetables onto a conveyor belt. Two cameras synchronized programmatically in the software interface simultaneously collected fluorescence and color image samples based on the region of interest as they moved through the conveyor belt. Using simple image processing algorithms, FMs could be detected and depicted in two different image windows. The results demonstrated that the dual imaging technique can effectively detect potential FMs in two types of fresh-cut vegetables (cabbage and green onion), as indicated by the combined fluorescence and color imaging accuracy. The test results showed that the real-time inspection system could detect FMs measuring 0.5 mm in fresh-cut vegetables. The results showed that the combined detection accuracy of FMs in the cabbage (95.77%) sample was superior to that of green onion samples (87.89%). Therefore, the inspection system was more effective at detecting FMs in cabbage samples than in green onion samples.

Anti-Streptococcus mutans and anti-inflammatory effects of ginsenoside Compound K and enzyme-treated red ginseng extract (BTEX-K).

OBJECTIVES: Dental caries, or tooth decay, is an oral health issue worldwide. Oral healthcare researchers are considering how to develop safe and effective preventive measures and treatments for dental caries. This study evaluated the potential applications of Compound K and BTEX-K, a Compound K-rich red ginseng extract, for the prevention and treatment of dental caries. Moreover, this study briefly confirmed its inhibitory effect on inflammation, an important factor in dental health. METHODS: The amount of organic acids produced by bacteria in biofilm was determined using in vitro and in vivo assays. The ability of these extracts to promote tooth remineralization and microhardness was evaluated using an in vivo mouse assay. We evaluated their anti-inflammatory potential by inhibiting proinflammatory cytokine expression and lipopolysaccharide-induced nitrous oxide production in cell lines. RESULTS: Compound K (10-20 µg/mL) and BTEX-K (50-100 µg/mL) effectively inhibited the growth of Streptococcus mutans bacteria, demonstrating significant antibacterial properties. They can potentially prevent biofilm formation by reducing lactic acid production in the teeth. These compounds showed a strong ability to promote tooth remineralization and improve the microhardness of acid-producing bacteria. They also possess potent anti-inflammatory properties that downregulate proinflammatory cytokine (interleukin-6, interleukin-1ß, inducible nitric oxide synthase) expression, suppress nuclear factor-kappa B transcription factor activation (∼1.6 times), and reduce nitrous oxide production in lipopolysaccharide-induced RAW264.7 cells. CONCLUSIONS: Compounds K and BTEX-K may provide a novel approach to dental caries prevention as well as inflammation prevention and treatment.

Systematic Proteome Profiling of Maternal Plasma for Development of Preeclampsia Biomarkers.

Preeclampsia (PE) is a hypertensive disorder of pregnancy with various clinical symptoms. However, traditional markers for the disease including high blood pressure and proteinuria are poor indicators of the related adverse outcomes. Here, we performed systematic proteome profiling of plasma samples obtained from pregnant women with PE to identify clinically effective diagnostic biomarkers. Proteome profiling was performed using TMT-based liquid chromatography-mass spectrometry (LC-MS/MS) followed by subsequent verification by multiple reaction monitoring (MRM) analysis on normal and PE maternal plasma samples. Functional annotations of differentially expressed proteins (DEPs) in PE were predicted using bioinformatic tools. The diagnostic accuracies of the biomarkers for PE were estimated according to the area under the receiver-operating characteristics curve (AUC). A total of 1307 proteins were identified, and 870 proteins of them were quantified from plasma samples. Significant differences were evident in 138 DEPs, including 71 upregulated DEPs and 67 downregulated DEPs in the PE group, compared with those in the control group. Upregulated proteins were significantly associated with biological processes including platelet degranulation, proteolysis, lipoprotein metabolism, and cholesterol efflux. Biological processes including blood coagulation and acute-phase response were enriched for down-regulated proteins. Of these, 40 proteins were subsequently validated in an independent cohort of 26 PE patients and 29 healthy controls. APOM, LCN2, and QSOX1 showed high diagnostic accuracies for PE detection (AUC >0.9 and p < 0.001, for all) as validated by MRM and ELISA. Our data demonstrate that three plasma biomarkers, identified by systematic proteomic profiling, present a possibility for the assessment of PE, independent of the clinical characteristics of pregnant women.

Tissue Mechanics and Hedgehog Signaling Crosstalk as a Key Epithelial-Stromal Interplay in Cancer Development.

Epithelial-stromal interplay through chemomechanical cues from cells and matrix propels cancer progression. Elevated tissue stiffness in potentially malignant tissues suggests a link between matrix stiffness and enhanced tumor growth. In this study, employing chronic oral/esophageal injury and cancer models, it is demonstrated that epithelial-stromal interplay through matrix stiffness and Hedgehog (Hh) signaling is key in compounding cancer development. Epithelial cells actively interact with fibroblasts, exchanging mechanoresponsive signals during the precancerous stage. Specifically, epithelial cells release Sonic Hh, activating fibroblasts to produce matrix proteins and remodeling enzymes, resulting in tissue stiffening. Subsequently, basal epithelial cells adjacent to the stiffened tissue become proliferative and undergo epithelial-to-mesenchymal transition, acquiring migratory and invasive properties, thereby promoting invasive tumor growth. Notably, transcriptomic programs of oncogenic GLI2, mechano-activated by actin cytoskeletal tension, govern this process, elucidating the crucial role of non-canonical GLI2 activation in orchestrating the proliferation and mesenchymal transition of epithelial cells. Furthermore, pharmacological intervention targeting tissue stiffening proves highly effective in slowing cancer progression. These findings underscore the impact of epithelial-stromal interplay through chemo-mechanical (Hh-stiffness) signaling in cancer development, and suggest that targeting tissue stiffness holds promise as a strategy to disrupt chemo-mechanical feedback, enabling effective cancer treatment.