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Analysis of the gut microbiome using extracellular vesicles in the urine of patients with colorectal cancer
Full text linkBackground/Aims: We evaluated the gut microbiome using extracellular vesicles (EVs) in the urine of patients with colorectal cancer (CRC) to determine whether gut-microbe-derived EVs could be a potential biomarker for the diagnosis of CRC. Methods: EVs were isolated from the urine of patients with CRC and healthy controls. DNA was extracted from the EVs, and the bacterial composition was analyzed using next-generation sequencing of the 16S rRNA. Results: A total of 91 patients with CRC and 116 healthy controls were enrolled. We found some specific microbiomes that were more or less abundant in the CRC group than in the control group. The alpha-diversity of the gut microbiome was significantly lower in the CRC group than in the control group. A significant difference was observed in the beta-diversity between the groups. The alpha-diversity indices between patients with early-and late-stage CRC showed conflicting results; however, there was no significant difference in the beta-diversity according to the stage of CRC. There was no difference in the alpha-and beta-diversity of the gut microbiome corresponding to the location of CRC (proximal vs. distal). Conclusions: A distinct gut microbiome is reflected in the urine EVs of patients with CRC compared with that in the healthy controls. Microbial signatures from EVs in urine could serve as potential biomarkers for the diagnosis of CRC. © 2023 The Korean Association of Internal Medicine.ope
Targeting AXL Using the AVB-500 Soluble Receptor and through Genetic Knockdown Inhibits Bile Duct Cancer Growth and Metastasis
Full text linkSimple Summary Bile duct cancer (cholangiocarcinoma) is a relatively rare cancer type that has a 5-year survival rate of 26% if diagnosed early, but a survival rate of less than 10% if the cancer has spread to the lymph nodes. Most patients with bile duct cancer are treated with surgery and chemotherapy, which unfortunately is more palliative than curative. In comparison to other gastrointestinal cancers, there are few targeted therapies which are specific to bile duct cancer. In searching for new molecular targets for bile duct cancer diagnosis and therapy, we found that the receptor tyrosine kinase AXL is highly expressed in bile duct cancer cells and that inhibition of its expression and signaling significantly reduces tumor growth and the spread of cancer cells. This study suggests that AXL is a potential new therapeutic target for treating bile duct cancers. Bile duct cancer, or cholangiocarcinoma, is a rare disease with limited treatment options that include surgery and cytotoxic chemotherapy. The high recurrence rate and poor prognosis of this type of cancer highlights the need to identify new and more effective therapeutic targets. In this study, we found that AXL, a receptor tyrosine kinase, is highly expressed in biliary cancer patients and significantly correlated with poor patient outcomes, including metastasis and low survival rates. We also demonstrated that targeting AXL inhibits tumor progression. In vitro studies with bile duct cancer cells (SNU1196 and HUCCT1) showed that genetic knockdown of AXL significantly reduced both tumor cell growth and invasion. In addition, in vivo studies using subcutaneous and orthotopic intrahepatic models demonstrated that genetic inhibition of AXL resulted in tumor-growth delay. To further examine the possible clinical translation of AXL inhibition in the clinic, we tested the efficacy of AVB-500, a soluble AXL receptor, in reducing AXL activation and tumor growth. AVB-500 was effective at inhibiting AXL activation and decreasing the growth and invasion of SNU1196 and HUCCT1 tumors which possess high AXL expression. Most importantly, AVB-500 was highly effective at decreasing tumor dissemination of bile duct tumor cells in the peritoneal cavity. This study strongly supports the idea of using the AXL receptor as a new therapeutic target to treat the growth and progression of biliary cancer.ope
Up to a 15-Year Survival Rate and Marginal Bone Resorption of 1780 Implants with or without Microthreads: A Multi Center Retrospective Study
Full text linkThe effect of microthreads at the implant neck on the amount of marginal bone resorption is controversial. This multicenter retrospective study compared the implant survival rate and amount of marginal bone resorption between two platform-switching internal connection implant systems with or without microthreads. Patient-related (age and sex), surgery-related (implant installation site, type, diameter, and length), and prosthesis-related (prosthesis type) data were collected from patient charts from the implant placement surgery to the final recall visit. A total of 1780 implants, including 1379 with microthreads and 401 without microthreads, were placed in 804 patients. For implants with and without microthreads, the longest follow-up period after prosthesis delivery was 15 and 6 years, respectively. Twenty implants failed during the 15-year follow-up period (98.8% survival rate) due to failed osseointegration, peri-implantitis, implant fractures, and non-functioning implants. The mean marginal bone loss was < 0.1 mm for both implant systems at the 1-year follow-up and 0.18 mm and 0.09 mm at the 4-year follow-up for implants with and without microthreads, respectively, without statistical significance. Microthreads did not significantly affect the amount of marginal bone loss or the implant survival rate for implants with an internal connection with a platform-switching design.ope
Neuroprotection: Rescue from Neuronal Death in the Brain 2.0
Full text linkThe brain is vulnerable to endogenous or exogenous injuries [...].ope
Risk factors based vessel-specific prediction for stages of coronary artery disease using Bayesian quantile regression machine learning method: Results from the PARADIGM registry
Full text linkBackground and HypothesisThe recently introduced Bayesian quantile regression (BQR) machine-learning method enables comprehensive analyzing the relationship among complex clinical variables. We analyzed the relationship between multiple cardiovascular (CV) risk factors and different stages of coronary artery disease (CAD) using the BQR model in a vessel-specific manner. MethodsFrom the data of 1,463 patients obtained from the PARADIGM (NCT02803411) registry, we analyzed the lumen diameter stenosis (DS) of the three vessels: left anterior descending (LAD), left circumflex (LCx), and right coronary artery (RCA). Two models for predicting DS and DS changes were developed. Baseline CV risk factors, symptoms, and laboratory test results were used as the inputs. The conditional 10%, 25%, 50%, 75%, and 90% quantile functions of the maximum DS and DS change of the three vessels were estimated using the BQR model. ResultsThe 90th percentiles of the DS of the three vessels and their maximum DS change were 41%-50% and 5.6%-7.3%, respectively. Typical anginal symptoms were associated with the highest quantile (90%) of DS in the LAD; diabetes with higher quantiles (75% and 90%) of DS in the LCx; dyslipidemia with the highest quantile (90%) of DS in the RCA; and shortness of breath showed some association with the LCx and RCA. Interestingly, High-density lipoprotein cholesterol showed a dynamic association along DS change in the per-patient analysis. ConclusionsThis study demonstrates the clinical utility of the BQR model for evaluating the comprehensive relationship between risk factors and baseline-grade CAD and its progression.ope
Mechanical properties of CAD/CAM polylactic acid as a material for interim restoration
Full text linkStatement of problem: Biomaterials, including polymethyl methacrylate (PMMA) and bisacrylate, have been widely used as conventional interim materials and may exhibit cytotoxicity or systemic toxicity.
Purpose: This study was designed to compare the mechanical properties of polylactic acid (PLA) as an alternative to conventional dental polymers for computer-aided design and manufacturing (CAD/CAM).
Material and methods: Four groups (n = 20 per group) of CAD/CAM polymers were assessed. Specimens of PLA (PLA Mill) and PMMA (PMMA Mill) for subtractive manufacturing, PLA for fused deposition modeling (PLA FDM), and bisphenol for additive manufacturing by stereo-lithography (Bisphenol SLA) were fabricated into 2-mm-wide, 2-mm-thick and 25-mm-long specimens using a milling machine, an FDM printer, and an SLA printer, respectively. The flexural strength (FS) and elastic modulus (EM) were calculated. The surface roughness and Shore D hardness were analyzed with a 3D optical surface roughness analyzer and a Shore durometer, respectively.
Results: PLA Mill showed the lowest FS (64.9 ± 8.28), followed by PLA FDM (104.27 ± 4.42 MPa), PMMA Mill (139.2 ± 20.95 MPa), and Bisphenol SLA (171.56 ± 15.38 MPa), with statistically significant differences. PLA FDM showed the highest EM, followed by PLA Mill, Bisphenol SLA, and PMMA Mill. Significant differences were observed not only between PMMA Mill and Bisphenol SLA but also between PLA FDM and PLA Mill. The lowest Shore D hardness was observed for PLA FDM, followed by PLA Mill, PMMA Mill, and Bisphenol SLA, which showed the highest value among the 4 groups, with significance. The highest values for the surface roughness parameters were observed for PLA Mill, and the lowest were observed for Bisphenol SLA.
Conclusions: Among the tested CAD/CAM polymers, Bisphenol SLA was the most durable material, and the mechanical properties of PLA FDM were within the clinically acceptable range.ope
Multistability and hysteresis in states of oral microbiota: Is it impacting the dental clinical cohort studies?
No full textIntroduction: Microbiome from a "healthy cohort" is used as a reference for comparison to cases and intervention. However, the studies with cohort-based clinical research have not sufficiently accounted for the multistability in oral microbial community. The screening is limited to phenotypic features with marked variations in microbial genomic markers. Herein, we aimed to assess the stability of the oral microbiome across time from an intervention-free "healthy" cohort.
Methods: We obtained 33 supragingival samples of 11 healthy participants from the biobank. For each participant, we processed one sample as baseline (T0) and two samples spaced at 1-month (T1) and 3-month (T2) intervals for 16S ribosomal RNA gene sequencing analysis.
Results: We observed that taxonomic profiling had a similar pattern of dominant genera, namely, Rothia, Prevotella, and Hemophilus, at all time points. Shannon diversity revealed a significant increase from T0 (p < .05). Bray Curtis dissimilarity was significant (R = -.02, p < .01) within the cohort at each time point. Community stability had negative correlation to synchrony (r = -.739; p = .009) and variance (r = -.605; p = .048) of the species. Clustering revealed marked differences in the grouping patterns between the three time points. For all time points, the clusters presented a substantially dissimilar set of differentially abundant taxonomic and functional biomarkers.
Conclusion: Our observations indicate towards the presence of multistable states within the oral microbiome in an intervention-free healthy cohort. For a conclusive and meaningful long-term reference, dental clinical research should account for multistability in the personalized therapy approach to improve the identification and classification of reliable markers.restrictio
Mechanoelectrical transduction-related genetic forms of hearing loss
No full textHair cells of the mammalian cochlea are specialized mechanosensory cells that convert mechanical stimuli into electrical signals to initiate the neuronal responses that lead to the perception of sound. The mechanoelectrical transduction (MET) machinery of cochlear hair cells is a multimeric protein complex that consists of the pore-forming subunits of the MET channel and several essential accessory subunits that are crucial to regulate channel function and render the channel mechanically sensitive. Mutations have been discovered in the genes that encode all known components of the MET machinery. These mutations cause hearing loss with or without vestibular dysfunction. Some mutations also affect other tissues such as the retina. In this brief review, we will summarize gene mutations that affect the MET machinery of hair cells and how the study of the affected genes has illuminated our understanding of the physiological role of the encoded proteins.restrictio
Androgen-Independent Prostate Cancer Is Sensitive to CDC42-PAK7 Kinase Inhibition
Full text linkProstate cancer is a common form of cancer in men, and androgen-deprivation therapy (ADT) is often used as a first-line treatment. However, some patients develop resistance to ADT, and their disease is called castration-resistant prostate cancer (CRPC). Identifying potential therapeutic targets for this aggressive subtype of prostate cancer is crucial. In this study, we show that statins can selectively inhibit the growth of these CRPC tumors that have lost their androgen receptor (AR) and have overexpressed the RNA-binding protein QKI. We found that the repression of microRNA-200 by QKI overexpression promotes the rise of AR-low mesenchymal-like CRPC cells. Using in silico drug/gene perturbation combined screening, we discovered that QKI-overexpressing cancer cells are selectively vulnerable to CDC42-PAK7 inhibition by statins. We also confirmed that PAK7 overexpression is present in prostate cancer that coexists with hyperlipidemia. Our results demonstrate a previously unseen mechanism of action for statins in these QKI-expressing AR-lost CRPCs. This may explain the clinical benefits of the drug and support the development of a biology-driven drug-repurposing clinical trial. This is an important finding that could help improve treatment options for patients with this aggressive form of prostate cancer. © 2022 by the authors.ope
Serotype Distribution and Antimicrobial Resistance of Streptococcus pneumoniae Causing Invasive Pneumococcal Disease in Korea Between 2017 and 2019 After Introduction of the 13-Valent Pneumococcal Conjugate Vaccine
Full text linkBackground: Streptococcus pneumoniae is a serious pathogen causing various infections in humans. We evaluated the serotype distribution and antimicrobial resistance of S. pneumoniae causing invasive pneumococcal disease (IPD) after introduction of pneumococcal conjugate vaccine (PCV)13 in Korea and investigated the epidemiological characteristics of multidrug-resistant (MDR) isolates.
Methods: S. pneumoniae isolates causing IPD were collected from 16 hospitals in Korea between 2017 and 2019. Serotyping was performed using modified sequential multiplex PCR and the Quellung reaction. Antimicrobial susceptibility tests were performed using the broth microdilution method. Multilocus sequence typing was performed on MDR isolates for epidemiological investigations.
Results: Among the 411 S. pneumoniae isolates analyzed, the most prevalent serotype was 3 (12.2%), followed by 10A (9.5%), 34 (7.3%), 19A (6.8%), 23A (6.3%), 22F (6.1%), 35B (5.8%), 11A (5.1%), and others (40.9%). The coverage rates of PCV7, PCV10, PCV13, and pneumococcal polysaccharide vaccine (PPSV)23 were 7.8%, 7.8%, 28.7%, and 59.4%, respectively. Resistance rates to penicillin, ceftriaxone, erythromycin, and levofloxacin were 13.1%, 9.2%, 80.3%, and 4.1%, respectively. MDR isolates accounted for 23.4% of all isolates. Serotypes 23A, 11A, 19A, and 15B accounted for the highest proportions of total isolates at 18.8%, 16.7%, 14.6%, and 8.3%, respectively. Sequence type (ST)166 (43.8%) and ST320 (12.5%) were common among MDR isolates.
Conclusions: Non-PCV13 serotypes are increasing among invasive S. pneumoniae strains causing IPD. Differences in antimicrobial resistance were found according to the specific serotype. Continuous monitoring of serotypes and antimicrobial resistance is necessary for the appropriate management of S. pneumoniae infections.ope