Although histone deacetylase 6 (HDAC6) is considered a therapeutic target for Alzheimer’s disease (AD), its role in cholinergic dysfunction in AD patients remains unclear. This study investigated the effects of (E)-3-(2-(4-fluorostyryl)thiazol-4-yl)-N-hydroxypropanamide (4-FHA), a new synthetic HDAC6 inhibitor, on cognitive and memory impairments in a scopolamine-induced-AD mouse model. Behaviorally, 4-FHA improved scopolamine-induced memory impairments in the Y-maze, passive avoidance, and Morris water maze tests. In addition, 4-FHA ameliorated scopolamine-induced cognitive impairments in the novel object recognition and place recognition tests. Furthermore, 4-FHA increased acetylation of α-tubulin (a major HDAC6 substrate); the expression of BDNF; and the phosphorylation of ERK 1/2, CREB, and ChAT in the hippocampus of scopolamine-treated mice. In summary, according to our data 4-FHA, an HDAC6 inhibitor, improved the cognitive and memory deficits of the AD mouse model by normalizing BDNF signaling and synaptic transmission, suggesting that 4-FHA might be a potential therapeutic candidate for AD.

Although histone deacetylase 6 (HDAC6) is considered a therapeutic target for Alzheimer’s disease (AD), its role in cholinergic dysfunction in AD patients remains unclear. This study investigated the effects of (E)-3-(2-(4-fluorostyryl)thiazol-4-yl)-N-hydroxypropanamide (4-FHA), a new synthetic HDAC6 inhibitor, on cognitive and memory impairments in a scopolamine-induced-AD mouse model. Behaviorally, 4-FHA improved scopolamine-induced memory impairments in the Y-maze, passive avoidance, and Morris water maze tests. In addition, 4-FHA ameliorated scopolamine-induced cognitive impairments in the novel object recognition and place recognition tests. Furthermore, 4-FHA increased acetylation of α-tubulin (a major HDAC6 substrate); the expression of BDNF; and the phosphorylation of ERK 1/2, CREB, and ChAT in the hippocampus of scopolamine-treated mice. In summary, according to our data 4-FHA, an HDAC6 inhibitor, improved the cognitive and memory deficits of the AD mouse model by normalizing BDNF signaling and synaptic transmission, suggesting that 4-FHA might be a potential therapeutic candidate for AD.

Although histone deacetylase 6 (HDAC6) is considered a therapeutic target for Alzheimer’s disease (AD), its role in cholinergic dysfunction in AD patients remains unclear. This study investigated the effects of (E)-3-(2-(4-fluorostyryl)thiazol-4-yl)-N-hydroxypropanamide (4-FHA), a new synthetic HDAC6 inhibitor, on cognitive and memory impairments in a scopolamine-induced-AD mouse model. Behaviorally, 4-FHA improved scopolamine-induced memory impairments in the Y-maze, passive avoidance, and Morris water maze tests. In addition, 4-FHA ameliorated scopolamine-induced cognitive impairments in the novel object recognition and place recognition tests. Furthermore, 4-FHA increased acetylation of α-tubulin (a major HDAC6 substrate); the expression of BDNF; and the phosphorylation of ERK 1/2, CREB, and ChAT in the hippocampus of scopolamine-treated mice. In summary, according to our data 4-FHA, an HDAC6 inhibitor, improved the cognitive and memory deficits of the AD mouse model by normalizing BDNF signaling and synaptic transmission, suggesting that 4-FHA might be a potential therapeutic candidate for AD.

Background/Aims: To compare the effects of abatacept and conventional synthetic disease modifying anti-rheumatic drugs (csDMARDs) on the progression and development of rheumatoid arthritis-associated interstitial lung disease (RA-ILD). Methods: This multi-center retrospective study included RA patients receiving abatacept or csDMARDs who underwent at least two pulmonary function tests and/or chest high-resolution computed tomography (HRCT). We compared the following outcomes between the groups: progression of RA-ILD, development of new ILD in RA patients without ILD at baseline, 28-joint Disease Activity Score with the erythrocyte sedimentation rate (DAS28-ESR), and safety. Longitudinal changes were compared between the groups by using a generalized estimating equation. Results: The study included 123 patients who were treated with abatacept (n = 59) or csDMARDs (n = 64). Nineteen (32.2%) and 38 (59.4%) patients treated with abatacept and csDMARDs, respectively, presented with RA-ILD at baseline. Newly developed ILD occurred in one patient receiving triple csDMARDs for 32 months. Among patients with RA-ILD at baseline, ILD progressed in 21.1% of cases treated with abatacept and 34.2% of cases treated with csDMARDs during a median 21-month follow-up. Longitudinal changes in forced vital capacity and diffusing capacity for carbon monoxide were comparable between the two groups. However, the abatacept group showed a more significant decrease in DAS28-ESR and glucocorticoid doses than csDMARDs group during the follow-up. The safety of both regimens was comparable. Conclusions Abatacept and csDMARDs showed comparable effects on the development and stabilization of RA-ILD. Nevertheless, compared to csDMARDs, abatacept demonstrated a significant improvement in disease activity and led to reduced glucocorticoid use.

Background/Aims: The microvascular invasion (MVI) of hepatocellular carcinoma (HCC) involves a wide histological spectrum, and it is unclear whether the degree of MVI correlates with patient prognosis or imaging findings. Here, we evaluate the prognostic value of MVI classification and analyze the radiologic features predictive of MVI. Methods: Using a retrospective cohort of 506 patients with resected solitary HCCs, the histological and imaging features of MVI were reviewed and correlated with clinical data. Results: MVI-positive HCCs invading ≥5 vessels or those with ≥50 invaded tumor cells were significantly associated with decreased overall survival (OS). The 5-year OS, recurrence-free survival (RFS), and beyond Milan criteria RFS rates were significantly poorer in patients with severe MVI compared with those with mild or no MVI. Severe MVI was a significant independent predictive factor for OS (odds ratio [OR], 2.962; p<0.001), RFS (OR, 1.638; p=0.002), and beyond Milan criteria RFS (OR, 2.797; p<0.001) on multivariable analysis. On MRI, non-smooth tumor margins (OR, 2.224; p=0.023) and satellite nodules (OR, 3.264; p<0.001) were independently associated with the severe-MVI group on multivariable analysis. Both non-smooth tumor margins and satellite nodules were associated with worse 5-year OS, RFS, and beyond Milan criteria RFS. Conclusions Histologic risk classification of MVI according to the number of invaded microvessels and invading carcinoma cells was a valuable predictor of prognosis in HCC patients. Non-smooth tumor margin and satellite nodules were significantly associated with severe MVI and poor prognosis.

Objective: To determine the prognostic value of MRI-based tumor regression grading (mrTRG) in rectal cancer compared withpathological tumor regression grading (pTRG), and to assess the effect of diffusion-weighted imaging (DWI) on interobserveragreement for evaluating mrTRG. Materials and Methods: Between 2007 and 2016, we retrospectively enrolled 321 patients (male:female = 208:113; meanage, 60.2 years) with rectal cancer who underwent both pre-chemoradiotherapy (CRT) and post-CRT MRI. Two radiologistsindependently determined mrTRG using a 5-point grading system with and without DWI in a one-month interval. Two pathologistsgraded pTRG using a 5-point grading system in consensus. Kaplan-Meier estimation and Cox-proportional hazard models wereused for survival analysis. Cohen’s kappa analysis was used to determine interobserver agreement. Results: According to mrTRG on MRI with DWI, there were 6 mrTRG 1, 48 mrTRG 2, 109 mrTRG 3, 152 mrTRG 4, and 6 mrTRG 5.By pTRG, there were 7 pTRG 1, 59 pTRG 2, 180 pTRG 3, 73 pTRG 4, and 2 pTRG 5. A 5-year overall survival (OS) was significantlydifferent according to the 5-point grading mrTRG (p= 0.024) and pTRG (p= 0.038). The 5-year disease-free survival (DFS)was significantly different among the five mrTRG groups (p= 0.039), but not among the five pTRG groups (p= 0.072). OSand DFS were significantly different according to post-CRT MR variables: extramural venous invasion after CRT (hazard ratio= 2.259 for OS, hazard ratio = 5.011 for DFS) and extramesorectal lymph node (hazard ratio = 2.610 for DFS). For mrTRG, kvalue between the two radiologists was 0.309 (fair agreement) without DWI and slightly improved to 0.376 with DWI. Conclusion mrTRG may predict OS and DFS comparably or even better compared to pTRG. The addition of DWI on T2-weightedMRI may improve interobserver agreement on mrTRG.

Daidzein isolated from soybean (Glycine max) has been widely studied for its antioxidant and anti-inflammatory activities. However, the protective effects of 7,8,4′-trihydroxyisoflavone (THIF), a major metabolite of daidzein, on 6-hydroxydopamine (OHDA)-induced neurotoxicity are not well understood. In the current study, 7,8,4′-THIF significantly inhibited neuronal cell death and lactate dehydrogenase (LDH) release induced by 6-OHDA in SH-SY5Y cells, which were used as an in vitro model of Parkinson's disease (PD). Moreover, pretreatment with 7,8,4′-THIF significantly increased the levels of superoxide dismutase (SOD), catalase (CAT), and glutathione (GSH) and decreased malondialdehyde (MDA) activity in 6-OHDA-induced SH-SY5Y cells. In addition, 7,8,4′-THIF significantly recovered 6-OHDA-induced cleaved caspase-3, cleaved caspase-9, cleaved poly-ADP-ribose polymerase (PARP), increased Bax, and decreased Bcl-2 levels. Additionally, 7,8,4′-THIF significantly restored the expression levels of phosphorylated c-Jun N-terminal kinase (JNK), p38 mitogen-activated protein kinase (MAPK), extracellular signal-regulated kinase 1/2 (ERK 1/2), phosphatidylinositol 3-kinases (PI3K)/Akt, and glycogen synthase kinase-3 beta (GSK-3β) in 6-OHDA-induced SH-SY5Y cells. Further, 7,8,4′-THIF significantly increased the reduced tyrosine hydroxylase (TH) level induced by 6-OHDA in SH-SY5Y cells. Collectively, these results suggest that 7,8,4′-THIF protects against 6-OHDA-induced neuronal cell death in cellular PD models. Also, these effects are mediated partly by inhibiting activation of the MAPK and PI3K/Akt/GSK-3β pathways.
Apoptosis ; Caspase 3 ; Caspase 9 ; Catalase ; Cell Death ; Glutathione ; Glycogen Synthase ; In Vitro Techniques ; JNK Mitogen-Activated Protein Kinases ; L-Lactate Dehydrogenase ; Malondialdehyde ; Neurons ; Oxidopamine ; Parkinson Disease ; Phosphatidylinositol 3-Kinases ; Phosphotransferases ; Protein Kinases ; Soybeans ; Superoxide Dismutase ; Tyrosine 3-Monooxygenase

The Committee of Clinical Practice Guidelines of the Korean Diabetes Association revised and updated the 6th Clinical Practice Guidelines in 2019. Targets of glycemic, blood pressure, and lipid control in type 2 diabetes mellitus (T2DM) were updated. The obese and overweight population is increasing steadily in Korea, and half of the Koreans with diabetes are obese. Evidence-based recommendations for weight-loss therapy for obesity management as treatment for hyperglycemia in T2DM were provided. In addition, evidence from large clinical studies assessing cardiovascular outcomes following the use of sodium-glucose cotransporter-2 inhibitors and glucagon-like peptide 1 receptor agonists in patients with T2DM were incorporated into the recommendations.
Blood Pressure ; Diabetes Mellitus, Type 2 ; Diagnosis ; Glucagon-Like Peptide 1 ; Humans ; Hyperglycemia ; Korea ; Obesity ; Overweight

OBJECTIVE: The purpose of this study was to asses the CT findings and clinical features differentiating malignant from benign focal splenic lesions. MATERIALS AND METHODS: Among 673 patients with splenectomy, we included 114 patients with pathologically confirmed focal splenic lesions (malignant = 66, benign = 48). Two radiologists retrospectively assessed CT findings including: size, number, solid component, margin, wall, calcification, contrast-enhancement, lymph node (LN) enlargement and possible malignancy. We assessed clinical features including age, sex, underlying malignancy, fever, and leukocytosis. Multivariate logistic regression analysis was performed to identify significant predictors of malignant lesion. We used receiver operating curve analysis for determination of diagnostic performance. RESULTS: Common findings of malignant lesions include enhanced, mainly solid, ill-defined margin, absence of splenomegaly, absence of the wall, absence of calcification, LN enlargement, and presence of underlying malignancy (p < 0.05). Among them, mainly solid features (odds ratio [OR], 39.098, p = 0.007), LN enlargement (OR, 6.326, p = 0.005), and presence of underlying malignancy (OR, 8.615, p = 0.001) were significant predictors of malignancy. The mean size of benign splenic lesions (5.8 ± 3.3 cm) was larger than that of malignant splenic lesions (4.0 ± 3.4 cm). Diagnostic performance of CT findings by two reviewers using receiver operating characteristic curve analysis for differentiation of malignant lesions was 0.856 and 0.893, respectively. CONCLUSION: Solid nature of the splenic mass on CT images, LN enlargement, and presence of underlying malignancy are significant predictors of malignant splenic lesion.
Equidae ; Fever ; Humans ; Leukocytosis ; Logistic Models ; Lymph Nodes ; Retrospective Studies ; ROC Curve ; Spleen ; Splenectomy ; Splenic Diseases ; Splenomegaly

OBJECTIVE: Investigation of initial 51 cases of single port access (SPA) laparoscopic surgery for large adnexal tumors and evaluation of safety and feasibility of the surgical technique. METHODS: We retrospectively reviewed the medical records of the first 51 patients who received SPA laparoscopic surgery for large adnexal tumors greater than 10 cm, from July 2010 to February 2015. RESULTS: SPA adnexal surgeries were successfully completed in 51 patients (100%). The mean age, body mass index of the patients were 43.1 years and 22.83 kg/m², respectively. The median operative time, median blood loss were 73.5 (range, 20 to 185) minutes, 54 (range, 5 to 500) mL, and the median tumor diameter was 13.6 (range, 10 to 30) cm. The procedures included bilateral salpingo-oophorectomy (n=18, 36.0%), unilateral salpingo-oophorectomy (n=14, 27.45%), and paratubal cystectomy (n=1, 1.96%). There were no cases of malignancy and none were insertion of additional ports or conversion to laparotomy. The cases with intraoperative spillage were 3 (5.88%) and benign cystic tumors. No other intraoperative and postoperative complications were observed during hospital days and 6-weeks follow-up period after discharge. CONCLUSION: Our results suggest that SPA laparoscopic surgery for large adnexal tumors may be a safe and feasible alternative to conventional laparoscopic surgery.
Body Mass Index ; Cystectomy ; Female ; Follow-Up Studies ; Humans ; Laparoscopy* ; Laparotomy ; Medical Records ; Minimally Invasive Surgical Procedures ; Operative Time ; Ovary ; Postoperative Complications ; Retrospective Studies