Arterial-Portal Venous Shunt after Drug-Eluting Bead Transarterial Chemoembolization for Hepatocellular Carcinoma Patients: Risk factors and Impact on Patient Survival.

INTRODUCTION: The effectiveness of transarterial chemoembolization (TACE) in treating hepatocellular carcinoma (HCC) has been well established. The differential impacts of drug-eluting bead TACE (DEB-TACE) as opposed to conventional TACE (cTACE) on vascular changes, such as arterial-portal venous shunts (APS), have been recognized. However, their subsequent effects on treatment outcomes have not been fully explored. This study aims to identify risk factors associated with the occurrence of APS in HCC patients treated with DEB-TACE and to evaluate its impact on patient survival. METHODS: A retrospective analysis was conducted from January 2012 to December 2018 including 74 HCC patients receiving DEB-TACE as initial treatment and a 1:1 conventional cTACE. Kaplan-Meier analysis estimated overall survival (OS) and progression-free survival (PFS). Logistic regression identified significant risk factors for APS occurrence after DEB-TACE. RESULTS: APS incidence was significantly higher after DEB-TACE than cTACE (46.0% vs. 16.2%, p < 0.001). No significant difference in median OS between APS and non-APS groups after DEB-TACE: 50 months (24.6-75.4) vs 26.9 months (19.5-43.2), p = 0.111; median PFS was 15.6 months (4.1-27.1) and 9.5 months (6.8-12.1) for the two groups, respectively, p = 0.065. Risk factors for APS occurrence after DEB-TACE were more than two feeding arteries (OR: 7.25, 95% CI: 1.82-28.95, p = 0.005) and non-selective embolization (OR: 8.02, 95% CI: 2.30-27.95, p = 0.001). CONCLUSION: APS occurrence was higher in DEB-TACE-treated HCC patients, but it did not significantly affect overall survival and progression free survival. More than two feeding arteries and non-selective embolization were significant risk factors for APS occurrence after DEB-TACE.

Comparison of Small (70-150 µm) and Intermediate (100-300 µm) Size Drug-Eluting Embolics for Transarterial Chemoembolization of Small Hepatocellular Carcinomas (≤3 cm).

PURPOSE: To compare oncologic outcomes of transarterial chemoembolization (TACE) using 70-150 µm and 100-300 µm drug-eluting beads (DEBs) to treat small hepatocellular carcinoma (HCC). METHODS: This retrospective study included 93 patients with small HCC (≤3cm) who underwent first TACE with DEB: 43 with 70-150 µm DEBs and 50 with 100-300 µm DEBs. Initial tumor response was assessed using per-patient and per-lesion analysis. Progression-free survival (PFS) and target tumor PFS were analyzed for patients and lesions with initial complete response (CR). Overall survival (OS) and safety outcomes were also evaluated. RESULTS: At 1 month, initial CR rates were 72.1% in the 70-150 µm group and 70.0% in the 100-300 µm group. PFS was significantly longer in the 70-150 µm group (median, 26 months) compared with the 100-300 µm group (median, 11 months; log-rank p=0.049), with comparable OS results (p=0.096). Per-lesion analysis found that target tumor PFS was significantly longer in the 70-150 µm group (median, 30 months) compared with the 100-300 µm group (median, 13 months; p=0.009). Subgroup analysis revealed the 70-150 µm group had significantly longer target tumor PFS compared with the 100-300 µm group in the 1.0-2.0 cm subgroup (p=0.017), but not in the 2.1-3.0 cm subgroup (p=0.117). No significant differences in adverse events were observed between the two groups. CONCLUSION: The 70-150 µm and 100-300 µm DEB-TACE resulted in comparable tumor response and short-term safety in small HCCs (≤3cm). However, in cases where CR was achieved, treatment with smaller beads demonstrated longer PFS and target tumor PFS.

Extracellular synthesis of silver nanoparticle using yeast extracts: antibacterial and seed priming applicationss.

The evolution and rapid spread of multidrug-resistant (MDR) bacterial pathogens have become a major concern for human health and demand the development of alternative antimicrobial agents to combat this emergent threat. Conventional intracellular methods for producing metal nanoparticles (NPs) using whole-cell microorganisms have limitations, including binding of NPs to cellular components, potential product loss, and environmental contamination. In contrast, this study introduces a green, extracellular, and sustainable methodology for the bio-materialization of silver NPs (AgNPs) using renewable resource cell-free yeast extract. These extracts serve as a sustainable, biogenic route for both reducing the metal precursor and stabilizing the surface of AgNPs. This method offers several advantages such as cost-effectiveness, environment-friendliness, ease of synthesis, and scalability. HR-TEM imaging of the biosynthesized AgNPs revealed an isotropic growth route, resulting in an average size of about ~ 18 nm and shapes ranging from spherical to oval. Further characterization by FTIR and XPS results revealed various functional groups, including carboxyl, hydroxyl, and amide contribute to enhanced colloidal stability. AgNPs exhibited potent antibacterial activity against tested MDR strains, showing particularly high efficacy against Gram-negative bacteria. These findings suggest their potential role in developing alternative treatments to address the growing threat of antimicrobial resistance. Additionally, seed priming experiments demonstrated that pre-sowing treatment with AgNPs improves both the germination rate and survival of Sorghum jowar and Zea mays seedlings. KEY POINTS: •Yeast extract enables efficient, cost-effective, and eco-friendly AgNP synthesis. •Biosynthesized AgNPs showed strong antibacterial activity against MDR bacteria. •AgNPs boost seed germination and protect against seed-borne diseases.

The Role of Prebiotics in Modulating Gut Microbiota: Implications for Human Health.

The human gut microbiota, an intricate ecosystem within the gastrointestinal tract, plays a pivotal role in health and disease. Prebiotics, non-digestible food ingredients that beneficially affect the host by selectively stimulating the growth and/or activity of beneficial microorganisms, have emerged as a key modulator of this complex microbial community. This review article explores the evolution of the prebiotic concept, delineates various types of prebiotics, including fructans, galactooligosaccharides, xylooligosaccharides, chitooligosaccharides, lactulose, resistant starch, and polyphenols, and elucidates their impact on the gut microbiota composition. We delve into the mechanisms through which prebiotics exert their effects, particularly focusing on producing short-chain fatty acids and modulating the gut microbiota towards a health-promoting composition. The implications of prebiotics on human health are extensively reviewed, focusing on conditions such as obesity, inflammatory bowel disease, immune function, and mental health. The review further discusses the emerging concept of synbiotics-combinations of prebiotics and probiotics that synergistically enhance gut health-and highlights the market potential of prebiotics in response to a growing demand for functional foods. By consolidating current knowledge and identifying areas for future research, this review aims to enhance understanding of prebiotics' role in health and disease, underscoring their importance in maintaining a healthy gut microbiome and overall well-being.

Regulation of Benzo[a]pyrene-Induced Hepatic Lipid Accumulation through CYP1B1-Induced mTOR-Mediated Lipophagy.

Metabolic dysfunction-associated steatotic liver disease (MASLD) is caused by lipid accumulation within the liver. The pathogenesis underlying its development is poorly understood. Benzo[a]pyrene (B[a]P) is a polycyclic aromatic hydrocarbon and a group 1 carcinogen. The aryl hydrocarbon receptor activation by B[a]P induces cytochrome P450 (CYP) enzymes, contributing to hepatic lipid accumulation. However, the molecular mechanism through which the B[a]P-mediated induction of CYP enzymes causes hepatic lipid accumulation is unknown. This research was conducted to elucidate the role of CYP1B1 in regulating B[a]P-induced lipid accumulation within hepatocytes. B[a]P increased hepatic lipid accumulation, which was mitigated by CYP1B1 knockdown. An increase in the mammalian target of rapamycin (mTOR) by B[a]P was specifically reduced by CYP1B1 knockdown. The reduction of mTOR increased the expression of autophagic flux-related genes and promoted phagolysosome formation. Both the expression and translocation of TFE3, a central regulator of lipophagy, were induced, along with the expression of lipophagy-related genes. Conversely, enhanced mTOR activity reduced TFE3 expression and translocation, which reduced the expression of lipophagy-related genes, diminished phagolysosome production, and increased lipid accumulation. Our results indicate that B[a]P-induced hepatic lipid accumulation is caused by CYP1B1-induced mTOR and the reduction of lipophagy, thereby introducing novel targets and mechanisms to provide insights for understanding B[a]P-induced MASLD.

Abutment margin levels and residual cement occurrence in cement-retained implant restorations: An observational study.

OBJECTIVES: To evaluate the association between different vertical levels of the abutment margin and residual cement prevalence in cement-retained implant restorations with customized abutments. METHODS: One hundred and nine single-unit cement-retained implant restorations with a screw-access channel were included. The crowns were intraorally cemented on the abutments, and excess cement was removed. The abutment-crown complex was unscrewed, and the abutment-crown complex and peri-implant tissue were photographed. Residual cement presence was recorded by dividing the abutment-crown complex and peri-implant tissue into four quadrants: mesial, distal, buccal, and lingual. The prevalence of residual cement was compared according to the height of the custom abutment margin of the corresponding quadrant. A multilevel model was used for statistical analysis (α = .05). RESULTS: Cement remnants were discovered on 72.48% of the dental implants. When the restoration quadrants were compared, cement remnants were present on 51.38%, 39.45%, 20.18%, and 17.43% of the mesial, distal, buccal, and lingual surfaces, respectively (p < .01). Regarding the abutment margin level, cement residues were found in 60.22% and 61.4% of the 0.5 mm subgingival and ≥1 mm subgingival margin groups, respectively, which were significantly more than those in the supragingival (23.65%) and equigingival (26.59%) margin groups (p < .01). After adjustment for confounding factors, the adjusted odds ratio (with 95% confidence interval) for residual cement in the subgingival margin groups was 3.664 (1.71, 7.852) when compared to the supragingival and equigingival margin groups. CONCLUSIONS: The risk of residual cement occurrence was 3.66-fold higher with a subgingival abutment margin than with supragingival and equigingival abutment margins.

Impact of aortoceliac angle in implantation of subcutaneous hepatic artery port-catheter system for hepatic arterial infusion chemotherapy via femoral approach.

BACKGROUND: In patients with an acute aortoceliac angle, the diagnostic catheter often fails to enter the common hepatic artery. PURPOSE: To retrospectively evaluate the impact of aortoceliac angle on the implantation of a port-catheter system via a femoral approach for hepatic arterial infusion chemotherapy (HAIC) in patients with advanced hepatocellular carcinoma (HCC). MATERIAL AND METHODS: A total of 399 patients with advanced HCC underwent percutaneous implantation of a port-catheter system for HAIC. Among these patients, 383 underwent successful implantation via a femoral artery approach (success group). In 16 patients, port-catheter systems were implanted via a subclavian artery approach (failure group) after failure of the initial attempt via the femoral artery due to failed catheter tip fixation to the gastroduodenal artery. We statistically analyzed aortoceliac angle, ostial celiac stenosis, sex, age, weight, height, and body mass index (BMI) between groups. RESULTS: The average aortoceliac angle, weight, and BMI were significantly different between the two groups (P < 0.001, P = 0.02, P < 0.001, respectively). Among them, only the aortoceliac angle was a significant risk factor in logistic regression analysis. The smaller the aortoceliac angle, the more often the femoral approach failed (P < 0.001, odds ratio = 0.817, 95% confidence interval = 0.752-0.887). There were no significant differences in ostial celiac stenosis, sex, or age between the two groups (P = 0.549, 0.056, 0.173, and 0.773, respectively). CONCLUSION: For patients with an acute aortoceliac angle, the femoral approach is likely to fail. A subclavian artery approach should be preferentially considered for percutaneous implantation of a port-catheter system in such patients.

Policresulen to treat hypergranulation tissue around drainage tubes.

OBJECTIVE: To evaluate the efficacy of policresulen for the treatment of hypergranulation. METHOD: This was a retrospective study of patients with percutaneous catheters. Inpatients from two hospitals and those from outpatient clinics were included. Approximately 2ml of 50% policresulen solution was applied to hypergranulation tissue, which was then immediately pressed with gauze for 1-3 minutes using light pressure. When haemostasis was achieved and the granulation tissue size decreased, the procedure was terminated. RESULTS: A total of eight patients (four females and four males) were included in this study. Effective haemostasis was achieved in all patients. The size of the hypergranulation tissue decreased with policresulen treatment, and resolved completely in one patient. There were no complications. Hypergranulation tissue recurred in one patient. Haemostasis was successfully achieved after repeated procedures. CONCLUSION: The findings of this study showed policresulen to be an inexpensive, easy treatment for hypergranulation at catheter insertion sites.

Development of Novel Tamsulosin Pellet-Loaded Oral Disintegrating Tablet Bioequivalent to Commercial Capsule in Beagle Dogs Using Microcrystalline Cellulose and Mannitol.

In this study, we developed a tamsulosin pellet-loaded orally disintegrating tablet (ODT) that is bioequivalent to commercially available products and has improved patient compliance using microcrystalline cellulose (MCC) and mannitol. Utilizing the fluid bed technique, the drug, sustained release (SR) layer, and enteric layer were sequentially prepared by coating MCC pellets with the drug, HPMC, Kollicoat, and a mixture of Eudragit L and Eudragit NE, respectively, resulting in the production of tamsulosin pellets. The tamsulosin pellet, composed of the MCC pellet, drug layer, SR layer, and enteric layer at a weight ratio of 20:0.8:4.95:6.41, was selected because its dissolution was equivalent to that of the commercial capsule. Tamsulosin pellet-loaded ODTs were prepared using tamsulosin pellets and various co-processed excipients. The tamsulosin pellet-loaded ODT composed of tamsulosin pellets, mannitol-MCC mixture, silicon dioxide, and magnesium stearate at a weight ratio of 32.16:161.84:4.0:2.0 gave the best protective effect on the coating process and a dissolution profile similar to that of the commercial capsule. Finally, no significant differences in beagle dogs were observed in pharmacokinetic parameters, suggesting that they were bioequivalent. In conclusion, tamsulosin pellet-loaded ODTs could be a potential alternative to commercial capsules, improving patient compliance.

Chronic Exposure to TDI Induces Cell Migration and Invasion via TGF-ß1 Signal Transduction.

Toluene diisocyanate (TDI) is commonly used in manufacturing, and it is highly reactive and causes respiratory damage. This study aims to identify the mechanism of tumorigenesis in bronchial epithelial cells induced by chronic TDI exposure. In addition, transcriptome analysis results confirmed that TDI increases transforming growth factor-beta 1 (TGF-ß1) expression and regulates genes associated with cancerous characteristics in bronchial cells. Our chronically TDI-exposed model exhibited elongated spindle-like morphology, a mesenchymal characteristic. Epithelial-mesenchymal transition (EMT) was evaluated following chronic TDI exposure, and EMT biomarkers increased concentration-dependently. Furthermore, our results indicated diminished cell adhesion molecules and intensified cell migration and invasion. In order to investigate the cellular regulatory mechanisms resulting from chronic TDI exposure, we focused on TGF-ß1, a key factor regulated by TDI exposure. As predicted, TGF-ß1 was significantly up-regulated and secreted in chronically TDI-exposed cells. In addition, SMAD2/3 was also activated considerably as it is the direct target of TGF-ß1 and TGF-ß1 receptors. Inhibiting TGF-ß1 signaling through blocking of the TGF-ß receptor attenuated EMT and cell migration in chronically TDI-exposed cells. Our results corroborate that chronic TDI exposure upregulates TGF-ß1 secretion, activates TGF-ß1 signal transduction, and leads to EMT and other cancer properties.

Color and surface stainability of additively and subtractively manufactured interim restorative materials against mouth rinses.

STATEMENT OF PROBLEM: Interim restorations are often used along with mouth rinses during the healing period following surgical procedures. However, evidence regarding the color and surface properties of digitally fabricated interim restorations after oral rinsing is lacking. PURPOSE: The purpose of this in vitro study was to evaluate whether different mouth rinses could affect the color and surface roughness of milled and printed interim restorations after simulated oral rinsing. MATERIAL AND METHODS: Disk-shaped specimens (Ø15×2 mm; N=180) were fabricated by using conventional (Jet Tooth Shade), milled (Yamahachi PMMA Disk), and printed (NextDent C&B) resin materials. All resin specimens were divided into 3 different groups according to the rinsing material: distilled water, whitening mouth rinse (Listerine Healthy White), and conventional mouth rinse (Listerine Cool Mint). The specimens were further allocated into short- and long-term subgroups, and oral rinsing simulation was performed (n=10). Short-term rinsing simulated the conditions in a usual interim restoration period, and long-term rinsing was performed to evaluate the properties of the interim materials. The color differences (CIEDE2000, ΔE00) between the baseline and each time point were determined by using a spectrophotometer. The surface roughness of the tested specimens was measured by using a confocal laser scanning microscope. Kruskal-Wallis and Friedman tests with nonparametric pairwise comparisons were used to analyze the data (α=.05). RESULTS: On simulation of a 6-month use of the mouth rinse, the color change in the milled resin did not differ from that in the conventional resin (P>.334), but the printed resin showed a significantly greater color change than the other resins (P<.007). The greatest color change with the printed resin was observed when a conventional mouth rinse was used. However, all color changes were below a perceptible threshold of 1.30. When daily rinsing for 14 years was simulated, all resin groups showed a perceptible color change when conventional mouth rinse was used, and the printed resin showed the greatest median ±interquartile range ΔE00 (2.24 ±0.2). In both short- and long-term simulations, the printed resin rinsed with the conventional mouth rinse showed significantly greater roughness than that rinsed with distilled water (P<.009). CONCLUSIONS: The printed resin showed higher stainability than the conventional resin, and the color change was greatest with the conventional mouth rinse. However, in 6 months of daily mouth rinse simulation, all the tested resin materials exhibited imperceptible color change and clinically acceptable surface roughness.

Psychometric properties of the Barriers Self-Efficacy Scale for Physical Activity-Korean.

This study examined the psychometric properties of the Barriers Self-Efficacy Scale-Physical Activity for Korean-speaking adults with osteoarthritis at risk for metabolic syndrome (N = 150). Factor analysis identified three dimensions of the Korean Barriers scale, explaining 65.9 % of the total variance. Confirmatory factor analysis indicated that the structural validity adequately fits the data. Construct validity confirmed significant associations between the amount of physical activity and psychological variables. The test-retest reliability was 0.87; the alpha was 0.90. The standardized response mean (0.497) indicated responsiveness to medium-magnitude change. The Korean Barriers scale can assess self-efficacy to engage in regular physical activity in clinical settings.

Does stress shielding after radial head arthroplasty affect functional outcomes?

BACKGROUND: Various complications related to the prosthesis, such as implant loosening and stress shielding phenomenon, could develop after prosthetic replacement of the radial head. Stress shielding is known to occur around rigidly fixed implants. The purpose of this study was to evaluate the clinical influence and causative factors of the stress shielding phenomenon after radial head arthroplasty (RHA). METHODS: Clinical records and radiographs of 56 patients with unreconstructable radial head fractures who received radial head replacement between 2009 and 2019 were reviewed. Exclusion criteria were infection, loosening, and follow-up of less than 24 months. After exclusion, 35 patients were enrolled. Patients were divided into two groups: an anatomical press-fit group (Anatomical Radial Head System; Acumed, Hillsboro, OR, USA) and a round bipolar cemented group (RHS; Tornier, Montbonnot Saint-Martin, France). Stress shielding around the prosthesis was assessed in the serial radiological examination. Clinical results were assessed using Mayo elbow performance score (MEPS), Quick Disabilities of the Arm, Shoulder, and Hand (q-DASH) score, range of motion (flexion-extension arc and pronation-supination arc), and visual analog scale score (VAS). Correlations between stress shielding phenomenon and demographic data and functional results were analyzed. RESULTS: At an average follow-up of 43.06 (± 14.6) months, 14 (40%) out of 35 fixed stems demonstrated stress shielding. Our results showed that the rate of stress shielding was significantly higher in cases with a bilateral ligament injury and in the anatomical press-fit group (p = 0.028 and p = 0.0091, respectively). However, stress shielding around prostheses did not affect the clinical results (p > 0.05). CONCLUSION: The stress shielding phenomenon around radial head prosthesis may vary according to prosthetic design and severity of ligament injuries. Stress shielding does not affect the mid-term outcomes in the treatment of acute fractures of the radial head. LEVEL OF EVIDENCE III: Retrospective Cohort Comparison; Treatment Study.

Interaction between Naegleria fowleri and pathogenic Escherichia coli by mannose and changes in N. fowleri protease.

Naegleria fowleri can cause acute primary amoebic encephalitis. It is known that contact-dependent pathogenicity in free-living amoeba may be mediated through a carbohydrate-dependent pathway. In this study, the effect of mannose on the interaction between N. fowleri and pathogenic Escherichia coli O157:H7 and non-pathogenic E. coli DH5α was analyzed. In particular, the changes in proteases expressed by N. fowleri in response to mannose were analyzed. Unlike the conventional method, mannose was treated with N. fowleri for 1 h. The association between N. fowleri and E. coli O157:H7 treated with 50-mM and 100-mM mannose was significantly reduced by approximately 70.9% and 128.5%, respectively. E. coli O157:H7 invasion was reduced by about 10.8% by 100-mM mannose. Moreover, as a result of culturing N. fowleri invaded by E. coli O157:H7 for 24 h, E. coli O157:H7 also grew about 1.2 times in the group not treated with mannose. E. coli DH5α association was reduced by 25.7% by 100-mM mannose. On the other hand, there was almost no inhibitory effect by 100-mM glucose. In the analysis in which mannose bound to either N. fowleri or bacteria and affected the interaction, there was little effect on the interaction between N. fowleri and bacteria. In zymographic analysis, about 135-kDa and 75-kDa bands were observed by 50-mM and 100-mM mannose, and two bands were significantly increased by 100-mM mannose. This study suggests that mannose can be mediated in the contact-dependent pathway of N. fowleri and will serve as a basis for inducing changes in the protease of N. fowleri by other monosaccharides.

Exposure of Toluene Diisocyanate Induces DUSP6 and p53 through Activation of TRPA1 Receptor.

Toluene diisocyanate (TDI), a major intermediate agent used in the manufacturing industry, causes respiratory symptoms when exposed to the human body. In this study, we aimed to determine the molecular mechanism of TDI toxicity. To investigate the impact of TDI exposure on global gene expression, we performed transcriptomic analysis of human bronchial epithelial cells (BEAS-2B) after TDI treatment. Differentially expressed genes (DEGs) were sorted and used for clustering and network analysis. Among DEGs, dual-specificity phosphatase 6 (DUSP6) was one of the genes significantly changed by TDI exposure. To verify the expression level of DUSP6 and its effect on lung cells, the mRNA and protein levels of DUSP6 were analyzed. Our results showed that DUSP6 was dose-dependently upregulated by TDI treatment. Thereby, the phosphorylation of ERK1/2, one of the direct inhibitory targets of DUSP6, was decreased. TDI exposure also increased the mRNA level of p53 along with its protein and activity which trans-activates DUSP6. Since TRPA1 is known as a signal integrator activated by TDI, we analyzed the relevance of TRPA1 receptor in DUSP6 regulation. Our data revealed that up-regulation of DUSP6 mediated by TDI was blocked by a specific antagonist against TRPA1. TDI exposure attenuated the apoptotic response, which suggests that it promotes the survival of cancerous cells. In conclusion, our results suggest that TDI induces DUSP6 and p53, but attenuates ERK1/2 activity through TRPA1 receptor activation, leading to cytotoxicity.

Quercetin and Isorhamnetin Reduce Benzo[a]pyrene-Induced Genotoxicity by Inducing RAD51 Expression through Downregulation of miR-34a.

Benzo[a]pyrene (B[a]P) is metabolized in the liver into highly reactive mutagenic and genotoxic metabolites, which induce carcinogenesis. The mutagenic factors, including B[a]P-7,8-dihydrodiol-9,10-epoxide (BPDE) and reactive oxygen species, generated during B[a]P metabolism can cause DNA damage, such as BPDE-DNA adducts, 8-oxo-dG, and double-strand breaks (DSBs). In this study, we mechanistically investigated the effects of quercetin and its major metabolite isorhamnetin on the repair of B[a]P-induced DNA DSBs. Whole-transcriptome analysis showed that quercetin and isorhamnetin each modulate the expression levels of genes involved in DNA repair, especially those in homologous recombination. RAD51 was identified as a key gene whose expression level was decreased in B[a]P-treated cells and increased by quercetin or isorhamnetin treatment. Furthermore, the number of γH2AX foci induced by B[a]P was significantly decreased by quercetin or isorhamnetin, whereas RAD51 mRNA and protein levels were increased. Additionally, among the five microRNAs (miRs) known to downregulate RAD51, miR-34a level was significantly downregulated by quercetin or isorhamnetin. The protective effect of quercetin or isorhamnetin was lower in cells transfected with a miR-34a mimic than in non-transfected cells, and the B[a]P-induced DNA DSBs remained unrepaired. Our results show that quercetin and isorhamnetin each upregulates RAD51 by downregulating miR-34a and thereby suppresses B[a]P-induced DNA damage.

De Novo Design of AC-P19M, a Novel Anticancer Peptide with Apoptotic Effects on Lung Cancer Cells and Anti-Angiogenic Activity.

Despite the current developments in cancer therapeutics, efforts to excavate new anticancer agents continue rigorously due to obstacles, such as side effects and drug resistance. Anticancer peptides (ACPs) can be utilized to treat cancer because of their effectiveness on a variety of molecular targets, along with high selectivity and specificity for cancer cells. In the present study, a novel ACP was de novo designed using in silico methods, and its functionality and molecular mechanisms of action were explored. AC-P19M was discovered through functional prediction and sequence modification based on peptide sequences currently available in the database. The peptide exhibited anticancer activity against lung cancer cells, A549 and H460, by disrupting cellular membranes and inducing apoptosis while showing low toxicity towards normal and red blood cells. In addition, the peptide inhibited the migration and invasion of lung cancer cells and reversed epithelial-mesenchymal transition. Moreover, AC-P19M showed anti-angiogenic activity through the inhibition of vascular endothelial growth factor receptor 2 signaling. Our findings suggest that AC-P19M is a novel ACP that directly or indirectly targets cancer cells, demonstrating the potential development of an anticancer agent and providing insights into the discovery of functional substances based on an in silico approach.

Effect of phytochemical-filled microcapsules with antifungal activity on material properties and dimensional accuracy of denture base resin for three-dimensional printing.

BACKGROUND: Studies on the material properties and dimensional accuracy of three-dimensionally (3D) printed denture base containing microcapsules with antifungal phytochemicals are lacking. METHODS: Two types of phytochemicals (phytoncide A and B) with antifungal activity were microencapsulated. The 3D-printed denture base specimens with minimum and maximum effective concentrations of microcapsules (6 and 8 wt% for phytoncide A; 15 and 25 wt% for phytoncide B) were prepared. The morphological changes of C. albicans on 3D-printed denture base with microcapsules was microscopically observed. The degree of conversion of 3D-printed denture base with microcapsules investigated. The microhardness and flexural strength values were also measured to evaluate the mechanical properties of 3D-printed denture bases. The dimensional accuracy (trueness) of the specimens with microcapsules was measured as root-mean-square values (RMS) for the whole, upper, and side surfaces of the specimens as well as their total height. For the degree of conversion, microhardness, and flexural strength values, the Kruskal-Wallis analysis and a post-hoc comparison using Mann-Whitney U test was performed. For the analysis of trueness (RMS), the one-way analysis of variance and a post-hoc comparison using Tukey's method was conducted (α = 0.05). RESULTS: At both maximum and minimum effective concentrations of microcapsules, cell surface disruption or membrane breakdown of fungal cells were observed in the specimens. The groups with microcapsules (both phytoncide A- and B-filled) showed significantly lower microhardness and elastic modulus values than the control group (all, P = 0.001). For the trueness, all the RMS values of the whole, upper, and side surfaces of the specimens with microcapsules were less than 100 µm, although significantly higher than those without (all, P = 0.001). The mean flexural strength values of the groups with phytoncide A-filled microcapsule were higher than 65 MPa, not statistically different from that of the control group (all, P > 0.05). However, the groups with phytoncide B-filled microcapsules showed significantly lower values than the control (all, P = 0.001). CONCLUSIONS: Within the limitations of this in-vitro study, the 3D-printed denture base containing 6 wt% of phytoncide A-filled microcapsules was clinically acceptable in terms of antifungal activity, dimensional accuracy, and flexural strength.

Production of a monoclonal antibody against a galactose-binding protein of Acanthamoeba castellanii and its cytotoxicity.

In this study, it was confirmed whether the galactose-binding protein (GBP) was present in Acanthamoeba castellanii, and its function on a target cell was confirmed by production of an antibody against the GBP. Since the genes for GBP have not yet been identified at all, the purification of GBP was done using galactose-beads from amoebial lysates, and monoclonal antibodies were produced using cell fusion. GBP was confirmed to have a size of about 35 kDa. After the third immunization with purified GBP in BALB/c mice, monoclonal antibody production was analyzed. The clone cultured before limiting dilution was named 2AB2 and showed the highest antibody titer in the culture supernatant of a 24-well plate. AF6 clone cultured after limiting dilution showed an antibody titer of 0.259 in a 75-T flask. Antibodies generated by collecting ascites by injecting monoclonal colonies into the abdominal cavity of mice were confirmed through gel analysis and were observed to belong to the isotype of the IgM having kappa chains. Since the cytotoxicity of A. castellanii was inhibited by about 26% by the monoclonal antibody against GBP, it was confirmed that the antibody against GBP had an inhibitory effect on cytotoxicity. This study was the first report on GBP isolated and purified from A. castellanii, and similarly to a mannose-binding protein (MBP), its involvement in contact-dependent cytotoxicity was demonstrated with monoclonal antibody production.

Comparable clinical and radiological outcomes between anatomical and high femoral tunnels in posterior cruciate ligament reconstruction.

PURPOSE: To compare clinical and radiological outcomes and failure rates between anatomical and high femoral tunnels in remnant-preserving single-bundle posterior cruciate ligament (PCL) reconstruction. METHODS: 63 patients who underwent remnant-preserving single-bundle PCL reconstruction between 2011 and 2018 with a minimum 2-year follow-up were retrospectively reviewed. Patients were divided into two groups according to the femoral tunnel position: group A (33 patients with anatomical femoral tunnel) and group H (30 patients with high femoral tunnels). The femoral tunnel was positioned at the center (group A) or upper margin (group H) of the remnant anterolateral bundle. The position of the femoral tunnel was evaluated using the grid method on three-dimensional computed tomography. Clinical and radiological outcomes and failure rates were compared between the groups at the 2-year follow-up. RESULTS: The position of the femoral tunnel was significantly high in group H than in group A (87.4% ± 4.2% versus 76.1% ± 3.7%, p < 0.001). Clinical outcomes were not significantly different between the two groups in terms of the clinical scores (International Knee Documentation Committee subjective, Lysholm, and Tegner activity scores), range of motion, and posterior drawer test. Radiological outcomes also showed no intergroup differences in the side-to-side differences of posterior tibial translation and osteoarthritis progression. Side-to-side difference on the Telos stress radiograph was 5.2 ± 2.9 mm in group A and 5.2 ± 2.7 mm in group H (n.s.). There were four failures in group A (12.1%) and one in group H (3.3%). The differences between the groups were not statistically significant. CONCLUSION: The clinical and radiological outcomes and failure rates of the high femoral tunnels were comparable with those of the anatomical femoral tunnels at the 2-year follow-up after remnant-preserving single-bundle PCL reconstruction. The findings of this study suggest that high femoral tunnels can be considered an alternative in remnant-preserving single-bundle PCL reconstruction. LEVEL OF EVIDENCE: III.