Manipulation of Macrophage Uptake by Controlling the Aspect Ratio of Graft Copolymer Micelles.

Nanostructures of drug carriers play a crucial role in nanomedicine due to their ability to influence drug delivery. There is yet no clear consensus regarding the optimal size and shape (e.g., aspect ratio) of nanoparticles for minimizing macrophage uptake, given the difficulties in controlling the shape and size of nanoparticles while maintaining identical surface properties. Here, we employed graft copolymer self-assembly to prepare polymer micelles with aspect ratios ranging from 1.0 (spherical) to 10.8 (cylindrical) and closely matched interfacial properties. Notably, our findings emphasize that cylindrical micelles with an aspect ratio of 2.4 are the least susceptible to macrophage uptake compared with both their longer counterparts and spherical micelles. This reduced uptake of the short cylindrical micelles results in a 3.3-fold increase in blood circulation time compared with their spherical counterparts. Controlling the aspect ratio of nanoparticles is crucial for improving drug delivery efficacy through better nanoparticle design.

Differential involvement of LUBAC-mediated linear ubiquitination in intestinal epithelial cells and macrophages during intestinal inflammation.

Disruption of the intestinal epithelial barrier and dysregulation of macrophages are major factors contributing to the pathogenesis of inflammatory bowel diseases (IBDs). Activation of NF-κB and cell death are involved in maintaining intestinal homeostasis in a cell type-dependent manner. Although both are regulated by linear ubiquitin chain assembly complex (LUBAC)-mediated linear ubiquitination, the physiological relevance of linear ubiquitination to intestinal inflammation remains unexplored. Here, we used two experimental mouse models of IBD (intraperitoneal LPS and oral dextran sodium sulfate [DSS] administration) to examine the role of linear ubiquitination in intestinal epithelial cells (IECs) and macrophages during intestinal inflammation. We did this by deleting the linear ubiquitination activity of LUBAC specifically from IECs or macrophages. Upon LPS administration, loss of ligase activity in IECs induced mucosal inflammation and augmented IEC death. LPS-mediated death of LUBAC-defective IECs was triggered by TNF. IEC death was rescued by an anti-TNF antibody, and TNF (but not LPS) induced apoptosis of organoids derived from LUBAC-defective IECs. However, augmented TNF-mediated IEC death did not overtly affect the severity of colitis after DSS administration. By contrast, defective LUBAC ligase activity in macrophages ameliorated DSS-induced colitis by attenuating both infiltration of macrophages and expression of inflammatory cytokines. Decreased production of macrophage chemoattractant MCP-1/CCL2, as well as pro-inflammatory IL-6 and TNF, occurred through impaired activation of NF-κB and ERK via loss of ligase activity in macrophages. Taken together, these results indicate that both intraperitoneal LPS and oral DSS administrations are beneficial for evaluating epithelial integrity under inflammatory conditions, as well as macrophage functions in the event of an epithelial barrier breach. The data clarify the cell-specific roles of linear ubiquitination as a critical regulator of TNF-mediated epithelial integrity and macrophage pro-inflammatory responses during intestinal inflammation. © 2022 The Pathological Society of Great Britain and Ireland.

Hepatoprotective Principles from the Rhizomes of Picrorhiza kurroa.

A methanol extract of rhizomes of Picrorhiza kurroa Royle ex Benth. (Plantaginaceae) showed hepatoprotective effects against D-galactosamine (D-GalN)/lipopolysaccharide (LPS)-induced liver injury in mice. We had previously isolated 46 compounds, including several types of iridoid glycosides, phenylethanoid glycosides, and aromatics, etc., from the extract. Among them, picroside II, androsin, and 4-hydroxy-3-methoxyacetophenone exhibited active hepatoprotective effects at doses of 50-100 mg/kg, per os (p.o.) To characterize the mechanisms of action of these isolates and to clarify the structural requirements of phenylethanoid glycosides for their hepatoprotective effects, their effects were assessed in in vitro studies on (i) D-GalN-induced cytotoxicity in mouse primary hepatocytes, (ii) LPS-induced nitric oxide (NO) production in mouse peritoneal macrophages, and (iii) tumor necrosis factor-α (TNF-α)-induced cytotoxicity in L929 cells. These isolates decreased the cytotoxicity caused by D-GalN without inhibiting LPS-induced macrophage activation and also reduced the sensitivity of hepatocytes to TNF-α. In addition, the structural requirements of phenylethanoids for the protective effects of D-GalN-induced cytotoxicity in mouse primary hepatocytes were evaluated.

A Turn-On Quinazolinone-Based Fluorescence Probe for Selective Detection of Carbon Monoxide.

Carbon monoxide (CO) is a toxic, hazardous gas that has a colorless and odorless nature. On the other hand, CO possesses some physiological roles as a signaling molecule that regulates neurotransmitters in addition to its hazardous effects. Because of the dual nature of CO, there is a need to develop a sensitive, selective, and rapid method for its detection. Herein, we designed and synthesized a turn-on fluorescence probe, 2-(2'-nitrophenyl)-4(3H)-quinazolinone (NPQ), for the detection of CO. NPQ provided a turn-on fluorescence response to CO and the fluorescence intensity at 500 nm was increased with increasing the concentration of CO. This fluorescence enhancement could be attributed to the conversion of the nitro group of NPQ to an amino group by the reducing ability of CO. The fluorescence assay for CO using NPQ as a reagent was confirmed to have a good linear relationship in the range of 1.0 to 50 µM with an excellent correlation coefficient (r) of 0.997 and good sensitivity down to a limit of detection at 0.73 µM (20 ppb) defined as mean blank+3SD. Finally, we successfully applied NPQ to the preparation of a test paper that can detect CO generated from charcoal combustion.

Efficacy and safety of atrial fibrillation ablation in heart failure patients with left ventricular ejection fraction less than 50.

INTRODUCTION: The efficacy of catheter ablation in patients with low cardiac function has been previously reported; however, only a few studies have included mid-range ejection fraction (mrEF). This study aimed to evaluate the efficacy and safety of atrial fibrillation (AF) ablation in patients with left ventricular ejection fraction (LVEF) < 50%. METHODS: This study retrospectively analyzed 79 patients (reduced ejection fraction [rEF]/mrEF, 38/41; paroxysmal/persistent, 37/42; heart failure hospitalizations within one year before ablation, 36 [45.6%]) who underwent the first ablation procedure at our hospital from April 2017 to December 2021. Radiofrequency ablation and cryoablation were performed for 69 and 10 patients, respectively. RESULTS: Complications included pacemaker implantation for postoperative sick sinus syndrome in one patient and inguinal hematoma in one patient. Regarding efficacy, there were significant postoperative improvements in echocardiographic data, blood test values, and diuretic use. After a mean follow-up of 60 months, 86.1% patients had no AF recurrence. There were 9 heart failure hospitalizations (11.4%) and 5 all-cause deaths (6.3%); no significant differences were found between the rEF and mrEF groups. No significant predictors of AF recurrence were found in preoperative patient characteristics. CONCLUSION: AF ablation in patients with LVEF <50% significantly improved cardiac and renal functions with few complications, resulting in a high non-recurrence rate and reduced heart failure.

Supramolecular Shear-Thinning Glycopeptide Hydrogels for Injectable Enzyme Prodrug Therapy Applications.

Transplantable catalytic reactors have attracted considerable attention as therapeutic biomedical materials. However, existing transplantable reactors such as biocatalytic films are limited by their invasiveness. Here, we report the fabrication of biocatalytic supramolecular hydrogels via self-assembly of amphiphilic glycopeptides. We show that the hydrogels have shear-thinning properties, demonstrating their potential to be administered using a syringe. Enzymes can be loaded into the hydrogels by simply adding enzyme solution, and the enzyme-loaded hydrogels can transform a prodrug into an anticancer drug that inhibits tumor cell growth. This study demonstrates the potential of these biocatalytic hydrogels as injectable therapeutic reactors for enzyme prodrug therapy.

Pharmacokinetics of CuGTSM, a Novel Drug Candidate, in a Mouse Model of Menkes Disease.

PURPOSE: Menkes disease is a rare hereditary disease in which systemic deficiency of copper due to mutation of the ATP7A gene causes severe neurodegenerative disorders. The present parenteral drugs have limited efficacy, so there is a need for an efficacious drug that can be administered orally. This study focused on glyoxal-bis (N(4)-methylthiosemicarbazonato)-copper(II (CuGTSM), which has shown efficacy in macular mice, a murine model of Menkes disease, and examined its pharmacokinetics. In addition, nanosized CuGTSM (nCuGTSM) was prepared, and the effects of nanosizing on CuGTSM pharmacokinetics were investigated. METHODS: CuGTSM or nCuGTSM (10 mg/kg) was administered orally to male macular mice or C3H/HeNCrl mice (control), and plasma was obtained by serial blood sampling. Plasma concentrations of CuGTSM and GTSM were measured by LC-MS/MS and pharmacokinetic parameters were calculated. RESULTS: When CuGTSM was administered orally, CuGTSM and GTSM were both detected in the plasma of both mouse strains. When nCuGTSM was administered, the Cmax was markedly higher, and the mean residence time was longer than when CuGTSM was administered for both CuGTSM and GTSM in both mouse strains. With macular mice, the AUC ratio (GTSM/CuGTSM) was markedly higher and the plasma CuGTSM concentration was lower than with C3H/HeNCrl mice when either CuGTSM or nCuGTSM was administered. CONCLUSION: Absorption of orally administered CuGTSM was confirmed in macular mice, and the nano-formulation improved the absorption and retention of CuGTSM in the body. However, the plasma concentration of CuGTSM was lower in macular mice than in control mice, suggesting easier dissociation of CuGTSM.

Early improvement of daily physical activity after catheter ablation for atrial fibrillation in an accelerometer assessment: A prospective pilot study.

BACKGROUND: Catheter ablation improves physical activity in patients with atrial fibrillation (AF). However, continuous daily evaluation and time course of improvement in physical activity after ablation have not been fully assessed. This prospective study was conducted to evaluate the daily physical activities and changes in the physical performance in patients undergoing catheter ablation for AF by continuous monitoring of a portable accelerometer. METHODS: Ten patients scheduled for catheter ablation for AF were fitted with a uniaxial accelerometer prior to and 6 months after the procedure. This study evaluated changes in daily steps, activity intensity, and activity duration. We also evaluated changes in activity intensity using a short version of the International Physical Activity Questionnaire (IPAQ). RESULTS: The maximum daily steps significantly increased from baseline to postablation (baseline, 9,232 [6,716-11,485]; after 1-3 months, 11,605 [8,285-14,802]; and after 4-6 months, 11,412 [8,939-13,808], p = .020). Similarly, Δ maximum-mean daily steps increased significantly (baseline, 2,431 [1,199-6,181]; after 1-3 months, 4,674 [4,164-6,474]; and after 4-6 months, 4,871 [3,657-6,117], p = .014). These improvements were more pronounced in patients with paroxysmal and symptomatic AF. The total IPAQ score significantly improved from baseline to after 6 months ablation (from 1,170 [693-3,930] to 4,312 [1,865-6,569], p = .037). All patients were recurrence-free from AF after ablation. CONCLUSIONS: The physical activity improved significantly even in the early phase following catheter ablation. The effect of suppressing AF on activity levels was apparent soon after the procedure.

Efficacy of isoproterenol in the evaluation of dormant conduction and arrhythmogenic foci identification in atrial fibrillation ablation.

BACKGROUND: Catheter ablation for atrial fibrillation (AF) is an established therapy. However, postoperative recurrence is a serious issue caused by the reconduction of the isolated pulmonary veins (PV) and the onset of non-PV foci. The objectives of this study were to elucidate dormant conduction, confirm PV arrhythmia substrate, induce non-PV foci after PV isolation, and assess the acute efficacy of high dose isoproterenol (ISP) when administered in addition to adenosine. METHODS: The study consisted of 100 patients with drug-refractory AF (paroxysmal and persistent) who underwent ablation therapy (either radio-frequency or cryoballoon ablation) as the first-line of therapy at our hospital. All patients first underwent PV isolation (PVI) and were administered adenosine followed by ISP (6 µg × 5 min). The effects were observed, and the therapeutic strategy was evaluated. RESULTS: Persistent dormant conduction due to ISP administration was observed in 13 patients. In over half of the patients, arrhythmia substrates were identified in the PV. Ten patients presented with persistent PV firing. The ablation of non-PV foci was additionally performed in 23 patients. CONCLUSIONS: We found that dormant conduction, as a result of ISP administration, is persistent and ISP is useful when performing an ablation. In addition, ISP administration is useful for the identification of PV arrhythmia substrates and induction of non-PV foci. However, the effectiveness of ISP may be partially due to the complementary effect of adenosine, and, therefore, a combination of the two drugs seems preferable.

The impact of the dominant frequency of body surface electrocardiography in patients with persistent atrial fibrillation.

The dominant frequency (DF) of atrial fibrillation (AF) reflects atrial electrical activity. However, the relationship between DF measured using surface electrocardiography (ECG) and AF ablation success remains unclear. This study aimed to clarify whether the DF of surface ECG in patients with persistent AF could predict arrhythmia recurrence after catheter ablation. We investigated 125 patients with persistent AF who underwent catheter ablation between January 2009 and December 2016. Thirty-four patients (27%) had arrhythmia recurrence after catheter ablation. These patients showed a significantly high DF value in leads aVL (7.2 ± 0.7 Hz vs 6.6 ± 0.9 Hz, p < 0.001) and V1 (7.4 ± 0.8 Hz vs 6.7 ± 0.7 Hz, p < 0.001). We set the cutoff value of DF as 6.9 Hz in lead aVL (sensitivity, 80%; specificity, 63%) and as 7.1 Hz in lead V1 (sensitivity, 72%; specificity, 67%). Patients with DF < 6.9 Hz in lead aVL showed a significantly higher recurrence-free rate than those with DF ≥ 6.9 Hz (88% vs 45%; p < 0.001). Patients with DF of < 7.1 Hz in lead V1 showed a significantly higher recurrence-free rate than those with DF of ≥ 7.1 (87% vs 47%; p < 0.001). Patients with a high DF in leads aVL and V1 showed a lower success rate of persistent AF ablation. The DF measured from surface ECG can be a useful marker to predict ablation success.

Electrocardiogram characteristics of P wave associated with successful pulmonary vein isolation in patients with paroxysmal atrial fibrillation: Significance of changes in P-wave duration and notched P wave.

BACKGROUND: The mechanisms involved in changes in P wave following catheter ablation for atrial fibrillation (AF) are uncertain. This study aimed to assess the relationship between changes in P-wave morphology and pulmonary vein (PV) reconnection following ablation by the assessment of 12-lead surface electrocardiogram and signal-averaged electrocardiogram. METHODS: This retrospective study included 115 consecutive patients with paroxysmal AF that underwent repeat ablation for recurrence following initial ablation. We investigated changes in P-wave morphology between baseline and repeat procedure in patients with and without PV reconnection. The study also included as validation group without recurrence (n = 67) following initial ablation. RESULTS: The maximum P-wave duration (PWD) was significantly decreased from baseline to just after the procedure in all groups. However, for the PV reconnection group (n = 100), the maximum PWD was significantly increased again at the repeat procedure. In contrast, the maximum PWD was significantly reduced between baseline and repeat procedure in the non-PV reconnection group (n = 15). The signal-averaged PWD was significantly decreased from baseline to repeat procedure in the non-PV reconnection group, but, conversely, was increased in the PV reconnection group. In the non-PV reconnection group, the disappearance of notched P wave was detected in 8 of 15 patients (53%), which was significantly higher than in other groups (p = .001). A new or delayed notched P wave was identified in the PV reconnection group only. These results were confirmed in the validation group. CONCLUSIONS: The reverse dynamics of PWD after initial shortening directly following ablation were significantly associated with PV reconnection.

T-wave changes of cardiac memory caused by frequent premature ventricular contractions originating from the right ventricular outflow tract.

INTRODUCTION: Cardiac memory is recognized as altered T-waves when the sinus rhythm resumes after an abnormal myocardial activation period that recovers slowly over several weeks. The T-wave changes after ablation of frequent premature ventricular contractions (PVCs) as cardiac memory was not known. OBJECTIVE: This study identified whether cardiac memory exists after successful ablation of PVCs from the right ventricular outflow tract (RVOT). METHODS: We investigated 45 patients who underwent successful ablation of PVCs from RVOT and 10 patients who underwent unsuccessful ablation. We analyzed the amplitude of the T-wave, QT intervals, and QRST time-integral values of a 12-lead electrocardiogram before ablation and 1 day, 3 days, and 1 month after ablation. RESULTS: In the successful ablation group, the amplitude of the T-wave and QRST time-integral values of lead II, III, aVR, aVL, and aVF significantly changed after ablation and gradually normalized within 1 month. In addition, if the number of pre-ablation PVCs was small, then the corresponding impact was also small. However, the greater the number of pre-ablation PVCs, the more prominent the changes. Significant changes were not observed in the unsuccessful ablation group. CONCLUSION: When ablation of PVCs from RVOT was successful, primary T-wave changes because of cardiac memory and the gradual normalization of the amplitude of the T-wave were observed. No significant T-wave changes were detected after unsuccessful ablation.

Myocardial viability as shown by left ventricular lead pacing threshold and improved dyssynchrony by QRS narrowing predicts the response to cardiac resynchronization therapy.

INTRODUCTION: Patients with advanced heart failure and dyssynchrony can benefit from cardiac resynchronization therapy (CRT). To predict the response to CRT, myocardial viability and improved dyssynchrony are suggested to be important. METHODS: We retrospectively investigated 93 patients who underwent CRT implantation in Nagoya University Hospital. We assessed QRS narrowing the day after implantation to measure the improvement in dyssynchrony and measured the left ventricular pacing threshold (LVPT) to determine the local myocardial viability in all patients. Responders to CRT were defined as those having a greater than or equal to 15% decrease in left ventricular end-systolic volume by echocardiography at their 6-month follow-up. RESULTS: Sixty-two patients (67%) were classified as responders. The QRS width before CRT implantation, QRS narrowing after implantation, left atrial diameter, septal-to-posterior wall motion delay, left ventricular end-diastolic diameter, radial strain, and LVPT were significantly different between the responder and nonresponder groups. On multivariate analysis, QRS narrowing (odds ratio [OR], 1.03; 95% confidence interval [CI], 1.01-1.05; P = 0.005) and LVPT (OR, 0.42; 95% CI, 0.22-0.82; P = 0.011) were independent predictors of a response to CRT. We calculated the cutoff values from the receiver operating characteristic curves as 22.5 milliseconds of QRS narrowing and 1.55 V of LVPT. The response rates in patients with both predictive factors (QRS narrowing ≥ 22.5 milliseconds and LVPT ≤ 1.55 V), one factor, and no factors were 91%, 61%, and 25%, respectively (P < 0.001). CONCLUSION: Both myocardial viability and improved electrical dyssynchrony may be essential to predict a good response to CRT.

Discontinuous contraction in the left ventricle assessed by 2-D speckle tracking echocardiography benefits from CRT.

BACKGROUND: Cardiac resynchronization therapy (CRT) improves the morbidity and mortality rate in patients with left bundle-branch block (LBBB); however, some LBBB patients are non-responders for CRT. Previous studies have shown that a transmural functional line block alters the left ventricular (LV) activation sequence, and that the presence of a line block is predictive for responders. We investigated whether responders could be predicted in patients with LBBB by 2-dimensional (2-D) speckle tracking strain imaging. METHODS: We enrolled 54 patients with LBBB, who underwent echocardiography before and 6 months after CRT implantation. A responder was defined by a decrease in the LV end-systolic volume >15% at the 6-month follow-up. We calculated a difference in the time from QRS onset to maximum strain between adjacent segments and defined the Tmax-diff as the maximum difference among six intersegments. We compared the Tmax-diff between responders and non-responders. RESULTS: Among 54 patients, 37 patients were identified as responders. The Tmax-diff of the responders was significantly longer than that of the non-responders (309.6 ± 168.6 ms vs 181.5 ± 138.4 ms, P = .009). Furthermore, Tmax-diff ≥ 195 ms was higher in the septal and the anterior area. And patients with a Tmax-diff ≥ 195 ms tended to be responders (P = .02). CONCLUSION: The present study showed that discontinuous contraction of the LV could be detected in CRT responders by 2-D speckle tracking strain imaging, which may be a useful tool to identify the contraction pattern of patients with LBBB and predict CRT responders.

Clinical significance of the timing of early recurrence of atrial arrhythmia after pulmonary vein isolation: a two-institution clinical study.

Early recurrence of atrial arrhythmia (ERAA) after ablation frequently occurs, but there is limited evidence about ERAA-timing. This study aimed to investigate the association between ERAA-timing and late recurrence. We retrospectively investigated 332 patients who underwent PVI for paroxysmal atrial fibrillation at Nagoya University Hospital and Komaki City Hospital. Seventy-six patients (23%) had ERAA. The cutoff value of the first ERAA for late recurrence was set as 3 days, with a specificity of 77% and sensitivity of 43%. On multivariate analysis, first ERAA beyond 3 days (hazard ratio, 2.477; 95% confidence interval, 1.168-5.25; p = 0.018) and large left atrial diameter (LAD) (hazard ratio, 1.101; 95% confidence interval, 1.024-1.184; p = 0.009) were independent predictors for late recurrence. Patients who had first ERAA within 3 days and no ERAA beyond 3 days showed a significantly higher recurrence-free rate than those who had first ERAA beyond 3 days and those who had ERAA both within 3 days and beyond 3 days (89% versus 39%, 44%; p < 0.001). Moreover, the patients with ERAA within 3 days and LAD ≤ 37.7 mm showed a significantly higher recurrence-free rate than those with ERAA beyond 3 days and LAD > 37.7 mm, and as compared with the other patients (100% versus 26% and 60%, respectively; p < 0.001). ERAA beyond 3 days after ablation was a predictor for late recurrence. Among patients with ERAA, those with ERAA within 3 days and smaller LAD showed favorable prognosis after ablation.

On the Functional Role of Valve Interstitial Cell Stress Fibers: A Continuum Modeling Approach.

The function of the heart valve interstitial cells (VICs) is intimately connected to heart valve tissue remodeling and repair, as well as the onset and progression of valvular pathological processes. There is yet only very limited knowledge and extant models for the complex three-dimensional VIC internal stress-bearing structures, the associated cell-level biomechanical behaviors, and how they change under varying activation levels. Importantly, VICs are known to exist and function within the highly dynamic valve tissue environment, including very high physiological loading rates. Yet we have no knowledge on how these factors affect VIC function. To this end, we extended our previous VIC computational continuum mechanics model (Sakamoto, et al., 2016, "On Intrinsic Stress Fiber Contractile Forces in Semilunar Heart Valve Interstitial Cells Using a Continuum Mixture Model," J. Mech. Behav. Biomed. Mater., 54(244-258)). to incorporate realistic stress-fiber geometries, force-length relations (Hill model for active contraction), explicit α-smooth muscle actin (α-SMA) and F-actin expression levels, and strain rate. Novel micro-indentation measurements were then performed using cytochalasin D (CytoD), variable KCl molar concentrations, both alone and with transforming growth factor ß1 (TGF-ß1) (which emulates certain valvular pathological processes) to explore how α-SMA and F-actin expression levels influenced stress fiber responses under quasi-static and physiological loading rates. Simulation results indicated that both F-actin and α-SMA contributed substantially to stress fiber force generation, with the highest activation state (90 mM KCL + TGF-ß1) inducing the largest α-SMA levels and associated force generation. Validation was performed by comparisons to traction force microscopy studies, which showed very good agreement. Interestingly, only in the highest activation state was strain rate sensitivity observed, which was captured successfully in the simulations. These unique findings demonstrated that only VICs with high levels of αSMA expression exhibited significant viscoelastic effects. Implications of this study include greater insight into the functional role of α-SMA and F-actin in VIC stress fiber function, and the potential for strain rate-dependent effects in pathological states where high levels of α-SMA occur, which appear to be unique to the valvular cellular in vivo microenvironment.

[A Case of Extragastric-Developing Gastric Cancer with Hepatic and Pancreatic Invasion Suggesting Squamous Differentiation].

A 69-year-old man presented with left upper abdominal pain and weight loss. Contrast-enhanced CT showed a 9 cmsized extragastric tumor located between the left lateral liver section and the gastric lesser curvature. Gastroendoscopy showed a type 3 tumor located at the lesser curvature of the antrum. Biopsy confirmed that the tumor was an adenocarcinoma. With a diagnosis of extragastric-developing gastric cancer with hepatic and pancreatic invasion, the patient underwent a totalgastrectomy, D2 lymph node dissection, partiall iver resection, and pancreatic body tailexcision. The pathologicaldiagnosis was poorly differentiated adenocarcinoma suggesting squamous differentiation. Despite receiving postoperative adjuvant chemotherapy, the patient died of recurrence 7 months later.

Time Course of Behavioral Alteration and mRNA Levels of Neurotrophic Factor Following Stress Exposure in Mouse.

Stress is known to affect neurotrophic factor expression, which induces depression-like behavior. However, whether there are time-dependent changes in neurotrophic factor mRNA expression following stress remains unclear. In the present study, we tested whether chronic stress exposure induces long-term changes in depression-related behavior, serum corticosterone, and hippocampal proliferation as well as neurotrophic factor family mRNA levels, such as brain-derived neurotrophic factor (BDNF), nerve growth factor (NGF), neurotrophin-3 (NT-3), and ciliary neurotrophic factor (CNTF), in the mouse hippocampus. The mRNA level of neurotrophic factors (BDNF, NGF, NT-3, and CNTF) was measured using the real-time PCR. The serum corticosterone level was evaluated by enzyme-linked immunosorbent assay, and, for each subject, the hippocampal proliferation was examined by 5-bromo-2-deoxyuridine immunostaining. Mice exhibited depression-like behavior in the forced-swim test (FST) and decreased BDNF mRNA and hippocampal proliferation in the middle of the stress exposure. After 15 days of stress exposure, we observed increased immobility in the FST, serum corticosterone levels, and BDNF mRNA levels and degenerated hippocampal proliferation, maintained for at least 2 weeks. Anhedonia-like behavior in the sucrose preference test and NGF mRNA levels were decreased following 15 days of stress. NGF mRNA levels were significantly higher 1 week after stress exposure. The current data demonstrate that chronic stress exposure induces prolonged BDNF and NGF mRNA changes and increases corticosterone levels and depression-like behavior in the FST, but does not alter other neurotrophic factors or performance in the sucrose preference test.

Comparison between anatomical subsegmentectomy and nonanatomical partial resection for hepatocellular carcinoma located within a single subsegment: a single-center retrospective analysis.

BACKGROUND/AIMS: For hepatocellular carcinoma (HCC) within a single subsegment, the superiority of anatomical subsegmentectomy over non-anatomical partial resection is still controversial. In this study, we assessed the potential benefit of subsegmentectomy. METHODOLOGY: We selected 44 patients with a single HCC lesion within one subsegment who had undergone anatomical subsegmentectomy or non-anatomical partial resection from among 173 patients who underwent hepatectomy in our hospital from August 2003 to May 2013. We compared the results following anatomical subsegmentectomy (Group A; n = 16) and non-anatomical partial resection (Group N; n = 28). RESULTS: One- and two-year survival rates were 92.5% and 89.3%, respectively; 1- and 2-year recurrence-free survival (RFS) rates were 88.9% and 69.1%, respectively. There was no significant difference in overall survival or RFS between the groups. However, among HBV-positive patients, RFS was significantly better for Group A than Group N (p = 0.008). CONCLUSIONS: For HBV-positive HCC within a single subsegment, we recommend subsegmentectomy.