Genetic Prediction of Smoking Cessation Medication Side Effects: A Genome-Wide Investigation of Abnormal Dreams on Varenicline.

Varenicline, the most efficacious smoking cessation monotherapy, produces abnormal dreams. Although genetic contributions to varenicline-associated nausea and cessation have been identified, the role of genetics in abnormal dreams is unknown. We conducted a genomewide association study (GWAS) of abnormal dreams in 188 European ancestry smokers treated with varenicline (NCT01314001). Additive genetic models examined the likelihood of experiencing abnormal dreams 2 weeks following varenicline initiation. For the top locus, we tested for selectivity to varenicline, effects on cessation, replication, and generalizability to African ancestry (AA) individuals. The top GWAS variant associated with abnormal dreams was rs901886, mapping to intron 2 of ICAM5 on chromosome 19. The prevalence of abnormal dreams in those with rs901886 CC, CT, and TT genotypes was 15%, 36%, and 62%, respectively (odds ratio = 2.94 for T vs. C, 95% confidence interval = 1.92-4.55, P = 2.03e-7; T allele frequency = 52%). This rs901886 association was selective to varenicline (P values > 0.05 on nicotine patch and placebo). There were also positive associations for rs901886 T (vs. C allele, P = 0.03) and for abnormal dreams (P = 0.06) with varenicline-aided cessation. Neither rs901886 (P = 0.40) nor abnormal dreams (P = 0.24) were associated with adherence. A similar direction of effect of rs901886 on abnormal dreams was observed in a second varenicline trial (NCT01836276). In AA individuals (n = 137), rs901886 was not associated with abnormal dreams (P = 0.41), but there was an association for a variant located ~ 74.4 kb 5' of ICAM5 (P = 2.56e-3). Variation in ICAM5 may influence abnormal dreams and cessation on varenicline. These findings provide additional support for genetically optimized smoking cessation approaches.

Assessment of potential ecological risk for polycyclic aromatic hydrocarbons in urban soils with high level of atmospheric particulate matter concentration.

Polycyclic aromatic hydrocarbons (PAHs) are known to be representative carcinogenic environmental pollutants with high toxicity. However, information on the potential ecological and environmental risks of PAH contamination in soil remains scarce. Thus, this study was evaluated the potential ecological risks of PAHs in soils of five Korean areas (Gunsan (GS), Gwangju, Yeongnam, Busan, and Gangwon) using organic carbon (OC)-normalized analysis, mean effect range-median quotient (M-ERM-Q), toxic equivalent quantity (TEQ) analysis, and risk quotient (RQ) derived by the species sensitivity distribution model. In this study, atmospheric particulate matter has a significant effect on soil pollution in GS through the presence of hopanes and the similar pattern of PAHs in soil and atmospheric PAHs. From analysis of source identification, combustion sources in soils of GS were important PAH sources. For PAHs in soils of GS, the OC-normalized analysis, M-ERM-Q, and TEQ analysis have 26.78 × 105 ng/g-OC, 0.218, and 49.72, respectively. Therefore, the potential ecological risk assessment results showed that GS had moderate-high ecological risk and moderate-high carcinogenic risk, whereas the other regions had low ecological risk and low-moderate carcinogenic risk. The risk level (M-ERM-Q) of PAH contamination in GS was similar to that in Changchun and Xiangxi Bay in China. The Port Harcourt City in Nigeria for PAH has the highest risk (M-ERM-Q = 4.02 and TEQ = 7923). Especially, compared to China (RQPhe =0.025 and 0.05), and Nigeria (0.059), phenanthrene showed the highest ecological risk in Korea (0.001-0.18). Korea should focus on controlling the release of PAHs originating from the PM in GS.

Biomechanical comparative finite element analysis between a conventional proximal interphalangeal joint flexible hinge implant and a novel implant design using a rolling contact joint mechanism.

BACKGROUND: The rolling contact joint (RCJ) mechanism is a system of constraint that allows two circular bodies connected with flexible straps to roll relative to one another without slipping. This study aims to compare the biomechanical characteristics between the conventional proximal interphalangeal joint (PIPJ) flexible hinge (FH) implant and the novel PIPJ implant adopting a RCJ mechanism during PIPJ range of motion using finite element (FE) analysis. METHODS: The three-dimensional (3D) surface shape of a conventional PIPJ FH implant was obtained using a 3D laser surface scanning system. The configuration and parameters of the novel PIPJ implant were adapted from a previous study. The two implants were assumed to have the same material characteristics and each implant was composed of a hyperelastic material, silicone elastomers. The configuration data for both implants were imported to a computer-aided design program to generate 3D geometrical surface and hyperelastic models of both implants. The hyperelastic models of both implants were imported into a structural engineering software to produce the FE mesh and to perform FE analysis. The FE analysis modeled the changes of mechanics during flexion-extension motion between 0° and 90° of two PIPJ implants. The mean and maximum values of von-Mises stress and strain as well as the total moment reaction based on the range of motion of the PIPJs were calculated. The mean values within the PIPJ's functional range of motion of the mean and maxinum von-Mises stress and strain and the total moment reaction were also determined. RESULTS: The maximum values for the von-Mises stress, and strain, as well as the total moment reactions of the conventional PIPJ FH and novel PIPJ implants were all at 90° of PIPJ flexion. The maximum value of each biomechanical property for the novel PIPJ implant was considerably lower compared with that of the conventional PIPJ FH implant. The mean values within the PIPJ's functional range of motion of the maximum von-Mises stress and strain for the novel PIPJ implant was approximately 6.43- and 6.46-fold lower compared with that of the conventional PIPJ FH implant, respectively. The mean value within a PIPJ's functional range of motion of the total moment reaction of the novel PIPJ implant was approximately 49.6-fold lower compared with that of the conventional PIPJ FH implant. CONCLUSIONS: The novel PIPJ implant with an RCJ mechanism may offer improved biomechanical performance compared with conventional PIPJ FH implant.

Mechanosensitive ion channels in apoptosis and ferroptosis: focusing on the role of Piezo1.

Mechanosensitive ion channels sense mechanical stimuli applied directly to the cellular membranes or indirectly through their tethered components, provoking cellular mechanoresponses. Among others, Piezo1 mechanosensitive ion channel is a relatively novel Ca2+-permeable channel that is primarily present in non-sensory tissues. Recent studies have demonstrated that Piezo1 plays an important role in Ca2+-dependent cell death, including apoptosis and ferroptosis, in the presence of mechanical stimuli. It has also been proven that cancer cells are sensitive to mechanical stresses due to higher expression levels of Piezo1 compared to normal cells. In this review, we discuss Piezo1-mediated cell death mechanisms and therapeutic strategies to inhibit or induce cell death by modulating the activity of Piezo1 with pharmacological drugs or mechanical perturbations induced by stretch and ultrasound. [BMB Reports 2023; 56(3): 145-152].

Outcomes of endovascular treatment for stenosis occurring after cephalic vein transposition and graft interposition.

OBJECTIVE: To evaluate the outcome of endovascular treatment after surgical treatment for cephalic arch stenosis (CAS) in the brachiocephalic fistula (BCF) and to analyze the factors influencing patency. METHODS: We conducted a retrospective review of patients undergoing cephalic vein transposition (CVT) or graft interposition (GIP) for CAS from January 1, 2017, to December 31, 2019. A total of 73 patients with restenosis were included in this study. Patients were classified into cephalic transposition (BCF-CVT) (n = 49) and graft interposition (BCF-GIP) (n = 24) groups. We calculated the postintervention primary and secondary patency of endovascular treatment by using the Kaplan-Meier analysis and analyzed variables associated with loss of postintervention patency. RESULTS: Six-month and 12-month postintervention primary patency rates of endovascular treatment for restenosis were 56.7% and 15.6% and secondary patency rates were 89.7% and 72.1%, respectively. In the BCF-CVT group, 6-month and 12-month postintervention primary patency was 56.8% and 17.6% and secondary patency was 93.3% and 79.4%, respectively. In the BCF-GIP group, 6-month and 12-month postintervention primary patency was 56.5% and 8.7% and secondary patency was 85.7% and 56.3%, respectively. There was no significant difference in postintervention primary patency between the two groups (P = .79). However, the BCF-CVT group demonstrated higher postintervention secondary patency (P = .034). The BCF-GIP group had a higher number of stenosis sites (P < .01). There was no significant predictor of reduced postintervention primary patency. The only adverse variable of postintervention secondary patency was BCF-GIP (hazard ratio, 3.14; 95% CI, 1.06-9.34; P < .05). CONCLUSIONS: Endovascular treatment is still the acceptable option for stenosis occurring after surgical treatment for CAS. CVT provides higher postintervention secondary patency than GIP.

Mitigation of Hematopoietic Syndrome of Acute Radiation Syndrome by 1-Palmitoyl-2-linoleoyl-3-acetyl-rac-glycerol (PLAG) is Associated with Regulation of Systemic Inflammation in a Murine Model of Total-Body Irradiation.

The growing risk of accidental radiation exposure due to increased usage of ionizing radiation, such as in nuclear power, industries and medicine, has increased the necessity for the development of radiation countermeasures. Previously, we demonstrated the therapeutic potential of the acetylated diacylglycerol, 1-palmitoyl-2-linoleoyl-3-acetyl-rac-glycerol (PLAG), as a radiation countermeasure by mitigating radiation-associated mortality and hematopoietic acute radiation syndrome (H-ARS) in BALB/c mice after a lethal dose (LD70/30) of gamma-ray total-body irradiation (TBI). In this study, we show that PLAG mitigates symptoms of H-ARS, as characterized by mature blood cell recovery and restoration of bone marrow cellularity, by regulating systemic inflammation. Log-rank test demonstrated that high levels of WBCs, lymphocytes and neutrophils on day 10 post-TBI resulted in significantly improved survival rate. PLAG significantly enhanced the nadir values of all major blood cell types as well as bone marrow cellularity. A single TBI at LD70/30 induced an immediate increase in the blood levels of CXCL1 (12.5 fold), CXCL2 (1.5 fold), IL-6 (86.9 fold), C-reactive protein (CRP; 1.3 fold) and G-CSF (15.7 fold) at 6 h post-TBI, but the cytokine levels returned to baseline level afterward. When the irradiated mice started to die around 15 days post-TBI, they exhibited a second surge in blood levels of CXCL1 (49.3 fold), CXCL2 (87.1 fold), IL-6 (208 fold), CRP (3.6 fold) and G-CSF (265.7 fold). However, PLAG-treated groups showed a significant decrease in these same blood levels (P < 0.001). Considering the inverse correlation between inflammatory cytokine levels and hematological nadirs, PLAG exerts its therapeutic effects on H-ARS by regulating inflammatory cytokine production. These data suggest that PLAG has high potential as a radiation countermeasure to mitigate H-ARS after accidental exposure to radiation.

Mitigating Effect of 1-Palmitoyl-2-Linoleoyl-3-Acetyl-Rac-Glycerol (PLAG) on a Murine Model of 5-Fluorouracil-Induced Hematological Toxicity.

5-Fluorouracil (5-FU) is an antimetabolite chemotherapy widely used for the treatment of various cancers. However, many cancer patients experience hematological side effects following 5-FU treatment. Here, we investigated the protective effects of 1-palmitoyl-2-linoleoyl-3-acetyl-rac-glycerol (PLAG) as a mitigator against 5-FU-induced hematologic toxicity, including neutropenia, monocytopenia, thrombocytopenia, and thrombocytosis, in Balb/c mice injected with 5-FU (100 mg/kg, i.p.). Administration of PLAG significantly and dose-dependently reduced the duration of neutropenia and improved the nadirs of absolute neutrophil counts (ANCs). Moreover, while the ANCs of all mice in the control fell to the severely neutropenic range, none of the mice in the PLAG 200 and 400 mg/kg-treated groups experienced severe neutropenia. Administration of PLAG significantly delayed the mean first day of monocytopenia and reduced the duration of monocytopenia. PLAG also effectively reduced extreme changes in platelet counts induced by 5-FU treatment, thus preventing 5-FU-induced thrombocytopenia and thrombocytosis. PLAG significantly decreased plasma levels of the chemokine (C-X-C motif) ligand 1 (CXCL1), CXCL2, interleukin (IL)-6, and C-reactive protein (CRP), which were elevated consistently with the occurrence time of neutropenia, monocytopenia, and thrombocytopenia. When compared with olive oil and palmitic linoleic hydroxyl glycerol (PLH), only PLAG effectively mitigated 5-FU-induced hematological toxicity, indicating that it has a distinctive mechanism of action. In conclusion, PLAG may have therapeutic potential as a mitigator for 5-FU-induced neutropenia and other hematological disorders.

Mitigating Effects of 1-Palmitoyl-2-linoleoyl-3-acetyl-rac-glycerol (PLAG) on Hematopoietic Acute Radiation Syndrome after Total-Body Ionizing Irradiation in Mice.

Acute radiation syndrome (ARS) occurs as a result of partial- or whole-body, high-dose exposure to radiation in a very short period of time. Survival is dependent on the severity of the hematopoietic sub-syndrome of ARS. In this study, we investigated the mitigating effects of a lipid molecule, 1-palmitoyl-2-linoleoyl-3-acetyl-rac-glycerol (PLAG), on the kinetics of hematopoietic cells, including absolute neutrophil count (ANC), red blood cells (RBCs) and platelet counts, in mice after gamma-ray total-body irradiation (TBI). Male and female BALB/c mice (11 weeks old) received a LD70/30 dose of TBI. PLAG significantly and dose-dependently attenuated radiation-induced mortality (P = 0.0041 for PLAG 50 mg/kg; P < 0.0001 for PLAG 250 mg/kg) and body weight loss (P < 0.0001 for PLAG 50 and 250 mg/kg) in mice. Single-fraction TBI sharply reduced ANC within 3 days postirradiation and maintained the neutropenic state (ANC < 500 cells/µl) by approximately 26.8 ± 0.8 days. However, administration of PLAG attenuated radiation-induced severe neutropenia (ANC < 100 cells/µl) by effectively delaying the mean day of its onset and decreasing its duration. PLAG also significantly mitigated radiation-induced thrombocytopenia (P < 0.0001 for PLAG 250 mg/kg) and anemia (P = 0.0023 for PLAG 250 mg/kg) by increasing mean platelet and RBC counts, as well as hemoglobin levels, in peripheral blood. Moreover, delayed administration of PLAG, even at 48 and 72 h after gamma-ray irradiation, significantly attenuated radiation-induced mortality in a time-dependent manner. When compared to olive oil and palmitic linoleic hydroxyl (PLH), only PLAG effectively attenuated radiation-induced mortality, indicating that it has a distinctive mechanism of action. Based on these preclinical observations, we concluded that PLAG has high potential as a radiation countermeasure for the improvement of survivability and the treatment of hematopoietic injury in gamma-ray-induced ARS.

Novel implant design of the proximal interphalangeal joint using an optimized rolling contact joint mechanism.

BACKGROUND: The aims of this study were to propose a novel implant design for the proximal interphalangeal joint (PIPJ) of the hand using a rolling contact joint (RCJ) mechanism and to derive an optimal implant design based on human PIPJ kinematics. METHODS: In total, 10 participants with normal PIPJs were enrolled in this study. True lateral finger radiographs were obtained in 10° increments from 0º (full extension) to 120° flexion of PIPJ. Radiographs were used to determine the average center of rotation, which formed the basis of a mathematical expression of the PIPJ kinematics. The variations in extensor tendon excursions in relation to the range of motion of PIPJ were determined using results from previous cadaveric studies. As the next step, a PIPJ implant design using an RCJ mechanism that was most consistent with the mathematically expressed PIPJ kinematics and tendon excursions was determined using a constrained optimization algorithm. RESULTS: The final proposed PIPJ implant had a relatively constant center of rotation over the entire PIPJ range of motion among the participants. In addition, the extensor tendon excursions of the proposed implant as applied to the phalangeal bones were similar to those of the human tendon. The proposed PIPJ implant achieved an acceptable position of the RCJ surface on the proximal and middle phalanges, which was derived from the constrained optimization algorithm. CONCLUSIONS: A novel PIPJ implant design using an RCJ mechanism demonstrated acceptable outcomes in terms of PIPJ human kinematics and tendon excursions.

Enhanced Selectivity of MXene Gas Sensors through Metal Ion Intercalation: In Situ X-ray Diffraction Study.

Gas molecules are known to interact with two-dimensional (2D) materials through surface adsorption where the adsorption-induced charge transfer governs the chemiresistive sensing of various gases. Recently, titanium carbide (Ti3C2T x) MXene emerged as a promising sensing channel showing the highest sensitivity among 2D materials and unique gas selectivity. However, unlike conventional 2D materials, MXenes show metallic conductivity and contain interlayer water, implying that gas molecules will likely interact in a more complex way than the typical charge transfer model. Therefore, it is important to understand the role of all factors that may influence gas sensing. Here, we studied the gas-induced interlayer swelling of Ti3C2T x MXene thin films and its influence on gas sensing performance. In situ X-ray diffraction was employed to simultaneously measure dynamic swelling behavior where Ti3C2T x MXene films displayed selective swelling toward ethanol vapor over CO2 gas. Results show that the controlling sodium ion concentration in the interlayers is highly important in tuning the swelling behavior and gas sensing performance. The degree of swelling matched well with the gas response intensity, and the highest gas selectivity toward ethanol vapor was achieved for Ti3C2T x sensing channels treated with 0.3 mM NaOH, which also displayed the largest amount of swelling. Our results demonstrate that controlling the interlayer transport of Ti3C2T x MXene is essential for enhancing the selective sensing of gas molecules.

A pancreatic hemorrhagic pseudocyst with pseudoaneurysm and the role of doppler ultrasonography: a case report.

Hemorrhagic pseudocysts with pseudoaneurysms are a rare and fatal complication of chronic pancreatitis due to the erosion of pancreatic to peripancreatic arteries. The timing of the rupture cannot be accurately predicted, but prompt diagnosis and management are essential to prevent further bleeding. We describe the case of a 68-year-old man who presented acute epigastric pain and anemia and had a history of chronic pancreatitis with a pseudocyst. A biliary and pancreas MRI showed an enlarged size of a known pancreatic pseudocyst with internal high signal intensity material. Color-Doppler ultrasonography showed pulsating signals in the pseudocyst, and our final diagnosis was a pseudoaneurysm in the pancreatic hemorrhagic pseudocyst. The pseudoaneurysm was successfully treated with coil embolization of the feeding artery. We report this case of a rare complication of chronic pancreatitis to show that color-Doppler ultrasound is a non-invasive and effective diagnostic tool for pseudoaneurysm, which enables early detection and prompt treatment without the need for invasive diagnostic modalities.

A pancreatic hemorrhagic pseudocyst with pseudoaneurysm and the role of doppler ultrasonography: a case report

SUMMARY Hemorrhagic pseudocysts with pseudoaneurysms are a rare and fatal complication of chronic pancreatitis due to the erosion of pancreatic to peripancreatic arteries. The timing of the rupture cannot be accurately predicted, but prompt diagnosis and management are essential to prevent further bleeding. We describe the case of a 68-year-old man who presented acute epigastric pain and anemia and had a history of chronic pancreatitis with a pseudocyst. A biliary and pancreas MRI showed an enlarged size of a known pancreatic pseudocyst with internal high signal intensity material. Color-Doppler ultrasonography showed pulsating signals in the pseudocyst, and our final diagnosis was a pseudoaneurysm in the pancreatic hemorrhagic pseudocyst. The pseudoaneurysm was successfully treated with coil embolization of the feeding artery. We report this case of a rare complication of chronic pancreatitis to show that color-Doppler ultrasound is a non-invasive and effective diagnostic tool for pseudoaneurysm, which enables early detection and prompt treatment without the need for invasive diagnostic modalities.

1-Palmitoyl-2-linoleoyl-3-acetyl-rac-glycerol (PLAG) attenuates gemcitabine-induced neutrophil extravasation.

Cancer patients treated with chemotherapy often experience a rapid decline of blood neutrophils, a dose-limiting side effect called chemotherapy-induced neutropenia. This complication brings about dose reductions or cessation of chemotherapy during treatment of cancer patients because a rapid decline of neutrophil counts increases susceptibility to infection. Here, we found that 1-palmitoyl-2-linoleoyl-3-acetyl-rac-glycerol (PLAG) attenuates gemcitabine-induced neutrophil extravasation via the inhibition of neutrophil-attracting chemokine production in macrophages using in vivo and in vitro approaches. A single intraperitoneal administration of gemcitabine induced the migration of circulating neutrophils into the peritoneal cavity in normal mice, and PLAG effectively decreased neutrophil migration by inhibiting the expression of adhesion molecules, L-selectin and LFA-1. Inhibition of CXCR2 by its antagonist, reparixin, abrogated gemcitabine-induced neutrophil migration, indicating that chemokines produced by gemcitabine mainly support neutrophil activation. In vitro experiments demonstrated that PLAG inhibited NADPH oxidase 2 (NOX2)-mediated reactive oxygen species production induced by gemcitabine, which is the upstream of MIP-2 and/or CXCL8. Importantly, PLAG down-regulated gemcitabine-induced membrane translocation of the cytosolic NOX subunit, Rac1, and phosphorylation of p47phox. The activation of upstream signaling molecules of p47phox phosphorylation, phospholipase C ß3 and protein kinase C, were effectively regulated by PLAG. We also demonstrated that 1-palmitoyl-2-linoleic-3-hydroxyl-rac-glycerol (PLH), the natural form of diacylglycerol, has no effects on gemcitabine-induced CXCL8 production and dHL-60 migration, suggesting that an acetyl group at the third position of the glycerol backbone may have a key role in the regulation of neutrophil activation. Altogether, this study suggests the potential of PLAG as a therapeutic strategy to modulate chemotherapy-induced neutrophil activation for cancer patients undergoing chemotherapeutic treatment.

Synergistic Effects of Sanghuang⁻Danshen Bioactives on Arterial Stiffness in a Randomized Clinical Trial of Healthy Smokers: An Integrative Approach to in silico Network Analysis.

The vascular endothelium is a favorite early target of cardiovascular risk factors, including cigarette smoking. Here, we investigated the synergistic effects of Sanghuang⁻Danshen (SD) bioactives on vascular stiffness in a controlled clinical trial of healthy chronic smokers (n = 72). Relative to placebo, 4-week SD consumption at 900 mg/day improves pulse wave velocity (p = 0.0497), reduces systolic blood pressure (peripheral, p = 0.0008; brachial, p = 0.0046; and ankle, p = 0.0066), and increases endothelial nitric oxide synthase activation (p < 0.0001). We then mapped all differential markers obtained from the clinical data, Affymetrix microarray, and ¹H NMR metabolomics, together with 12 SD bioactives, onto the network platform termed the context-oriented directed associations. The resulting vascular subnetwork demonstrates that ellagic acid, caffeic acid, protocatechuic acid, cryptotanshinone, tanshinone I, and tanshinone IIA are linked to NOS3, ARG2, and EDN1 for vascular dilation, implicated with arginine/proline metabolism. They are also linked to SUCLG1, CYP1A1, and succinate related to the mitochondrial metabolism and detoxification, implicated with various metabolic pathways. These results could explain the synergistic action mechanisms of SD bioactives in the regulation of vascular endothelial dilation and metabolism, confirming the potential of SD in improving vascular stiffness and blood pressure in healthy smokers.

Clinical outcomes of patients with a single hepatocellular carcinoma less than 5 cm treated with transarterial chemoembolization.

BACKGROUND/AIMS: Transarterial chemoembolization (TACE) is performed for single hepatocellular carcinoma (HCC) that are not eligible for surgery or ablation therapy. We investigated the clinical outcomes of patients with a single HCC ≤ 5 cm treated with TACE. METHODS: This study analyzed 175 consecutive patients who underwent TACE as an initial treatment for single HCC ≤ 5 cm. Predictive factors for complete response (CR), recurrence after CR, and overall survival (OS) were evaluated. RESULTS: Total 119 patients (68%) achieved CR after TACE. Tumor size < 3 cm and hepatitis B virus infection were significant predictors of CR (p < 0.05). Recurrent HCC was detected in 73 patients (61.3%) after CR. Age > 65 years and absence of liver cirrhosis were predictive factors for non-recurrence after CR (p < 0.05). The OS for all patients was 80.7 ± 5.6 months, and the 1-, 3-, and 5-year OS rates were 88.1%, 64.8%, and 49.9%, respectively. In multivariate analysis for OS, CR (hazard ratio [HR], 0.467; 95% confidence interval [CI], 0.292 to 0.747) and Child class A (HR, 0.390; 95% CI, 0.243 to 0.626) were significant factors. The OS for the CR and Child class A group were 92 and 93.6 months, respectively, and that of the non-CR and Child B, C group were 53.3 and 50.7 months, respectively (p < 0.001). CONCLUSION: TACE can be a valid treatment in patients with a single HCC ≤ 5 cm not suitable for curative treatment, especially in patients with Child class A and CR after TACE.

A 13-week subchronic toxicity study of an Eriobotrya japonica leaf extract in rats.

ETHNOPHARMACOLOGICAL RELEVANCE: Eriobotrya japonica leaf is widely used in traditional medicine, and exhibits various beneficial effects such as anti-inflammatory, antiviral, antioxidant, and antitumor activities. However, limited data are available on the potential adverse effects of E. japonica. AIM OF THE STUDY: This study investigated the potential subchronic toxicity of an E. japonica leaf extract (EJE) through a 13-week repeated oral dose experiment in Sprague-Dawley rats. MATERIALS AND METHODS: Forty male and 40 female rats were randomly assigned to four experimental groups: three treatment groups receiving 250, 500, and 1000 mg/kg/day of EJE and a vehicle control group receiving sterile distilled water for 13 weeks. RESULTS: Repeated oral administration of EJE for 13 weeks did not cause any treatment-related adverse effects with respect to clinical symptoms, body weight, food and water consumption, urinalysis, ophthalmology, necropsy findings, hematology, serum biochemistry, organ weight, and histopathological examination at any dose tested. Although some changes were observed in clinical symptoms, organ weight, hematology, and histopathology, these findings did not show a dose-response relationship and were within normal historical ranges for control rats. CONCLUSION: Under the present experimental conditions, the no-observed-adverse-effect level of EJE was > 1000 mg/kg/day in both sexes and no target organs were identified. The results suggest that the EJE is a safe traditional medicine for clinical applications at proper dose.

T3SS effector ExoY reduces inflammasome-related responses by suppressing bacterial motility and delaying activation of NF-κB and caspase-1.

Type III-secreted effectors are essential for modulating host immune responses during the pathogenesis of Pseudomonas aeruginosa infections. Little is known about the impact of one of the effectors, ExoY, on inflammasome activation, which results in IL-1ß production and pyroptotic cell death. In this study, we found that transcriptional expression of Il-1ß was induced to a lesser extent in response to an exoY-harboring strain than to a deleted mutant. This suppressive effect of ExoY was verified by complementation assay as well as by direct translocation of exoY into host cells. In addition to the production of IL-1ß, pyroptotic cell death was also diminished in response to an exoY-harboring strain. These inflammasome responses were mediated by the adenylate cyclase activity of ExoY, which plays a role in delaying the activation of NF-κB and caspase-1, a key component of inflammasome-mediated responses. Moreover, the negative effects of ExoY on these responses were in part conferred by the suppression of bacterial motility, which could reduce the degree of bacterial contact with cells. Together, these results demonstrate that the adenylate cyclase activity of P. aeruginosa ExoY can reduce inflammasome-related responses by influencing both the host and the bacterium itself by delaying the activation of inflammatory pathways and suppressing bacterial motility.

Lotus (Nelumbo nucifera) Rhizome as an Antioxidant Dietary Fiber in Cooked Sausage: Effects on Physicochemical and Sensory Characteristics.

The objective of this study was to determine the physicochemical and sensory properties of cooked emulsion sausages containing different levels of lotus rhizome powder (0, 1, 2, and 3%, based on total weight). Lotus rhizome powder had no significant (p>0.05) impact on pH, moisture, protein, or ash content of sausage. However, fat content was slightly but significantly (p<0.05) decreased when the level of lotus rhizome powder was increased in the sausages. The addition of lotus rhizome powder to sausages at over 1% resulted in significantly (p<0.05) darker and less red color of cooked sausage compared to control. Increase in lotus rhizome level slightly improved the emulsion stability and apparent viscosity. Significant (p<0.05) reduction in cooking loss was observed when more than 1% of lotus rhizome powder was added to sausages. The textural properties of sausages were unaffected by the inclusion of lotus rhizome except for springiness and chewiness. On the manufacture day, control sausage had significantly (p<0.05) higher TBARS value than treatments. Regarding sensory characteristics, increased levels of lotus rhizome powder decreased (p<0.05) color and juiciness scores. However, cooked sausages exhibited similar overall acceptability regardless of the level of lotus rhizome powder added to sausages. Therefore, lotus rhizome powder, an antioxidant dietary fiber, could be used as an effective natural ingredient in meat products for the development of healthier and functional food.

Predictive Factors for Complete Response and Recurrence after Transarterial Chemoembolization in Hepatocellular Carcinoma.

BACKGROUND/AIMS: To investigate the predictive factors for complete response (CR) and recurrence after CR in patients with hepatocellular carcinoma (HCC) treated with transarterial chemoembolization (TACE). METHODS: Among 691 newly diagnosed HCC patients, 287 were treated with TACE as a first therapy. We analyzed the predictive factors for CR, recurrence after CR, and overall survival (OS). RESULTS: Eighty-one patients (28.2%) achieved CR after TACE, and recurrence after CR was detected in 35 patients (43.2%). In multivariate analyses, tumor size (≤5 cm) and single nodularity were predictive factors for CR, with hazard ratios (HRs) of 0.35 (p=0.002) and 0.41 (p<0.001), respectively. Elevated serum α-fetoprotein (AFP) (>20 ng/mL) level and multinodularity exhibited significant relationships with recurrence after CR, with HRs of 2.220 (p=0.026) and 3.887 (p<0.001), respectively. Tumor size (>5 cm), multinodularity, elevated serum AFP (>20 ng/mL) level, Child-Turcotte-Pugh score (B and C), and portal vein thrombosis were significant factors for OS. CONCLUSIONS: In patients treated with TACE as a first therapy, tumor size (≤5 cm) and single nodularity were predictive factors for CR, and multinodularity and elevated serum AFP (>20 ng/mL) levels were predictive factors for recurrence after CR. These factors were also significant for OS.

Diagnostic accuracy of transabdominal high-resolution US for staging gallbladder cancer and differential diagnosis of neoplastic polyps compared with EUS.

PURPOSE: To compare the diagnostic accuracy of transabdominal high-resolution ultrasound (HRUS) for staging gallbladder cancer and differential diagnosis of neoplastic polyps compared with endoscopic ultrasound (EUS) and pathology. MATERIALS AND METHODS: Among 125 patients who underwent both HRUS and EUS, we included 29 pathologically proven cancers (T1 = 7, T2 = 19, T3 = 3) including 15 polypoid cancers and 50 surgically proven polyps (neoplastic = 30, non-neoplastic = 20). We reviewed formal reports and assessed the accuracy of HRUS and EUS for diagnosing cancer as well as the differential diagnosis of neoplastic polyps. Statistical analyses were performed using chi-square tests. RESULTS: The sensitivity, specificity, PPV, and NPV for gallbladder cancer were 82.7 %, 44.4 %, 82.7 %, and 44 % using HRUS and 86.2 %, 22.2 %, 78.1 %, and 33.3 % using EUS. HRUS and EUS correctly diagnosed the stage in 13 and 12 patients. The sensitivity, specificity, PPV, and NPV for neoplastic polyps were 80 %, 80 %, 86 %, and 73 % using HRUS and 73 %, 85 %, 88 %, and 69 % using EUS. Single polyps (8/20 vs. 21/30), larger (1.0 ± 0.28 cm vs. 1.9 ± 0.85 cm) polyps, and older age (52.5 ± 13.2 vs. 66.1 ± 10.3 years) were common in neoplastic polyps (p < 0.05). CONCLUSION: Transabdominal HRUS showed comparable accuracy for diagnosing gallbladder cancer and differentiating neoplastic polyps compared with EUS. HRUS is also easy to use during our routine ultrasound examinations. KEY POINTS: • HRUS showed comparable diagnostic accuracy for GB cancer compared with EUS. • HRUS and EUS showed similar diagnostic accuracy for differentiating neoplastic polyps. • Single, larger polyps and older age were common in neoplastic polyps. • HRUS is less invasive compared with EUS.