BACKGROUND/OBJECTIVES: Atherosclerosis is a primary cause of cardiovascular disease associated with inflammation and lipid metabolism disorders. The accumulation of cholesterol-containing macrophage foam cells characterizes the early stages. The p-coumaric acid (p-CA) contained in vegetables may have various physiological activities. The inhibitory effect of p-CA on foam cell creation in THP-1 macrophages needs clarification. In this study, we explored the impact of p-CA on foam cells by co-treatment with oxidized lowdensity lipoprotein (ox-LDL) and lipopolysaccharides (LPS), mimicking the development of atherosclerosis in vitro and studied the regulation of its underlying mechanisms.MATERIALS/METHODS: THP-1 cells differentiated by phorbol 12-myristate 13-acetate (1 μM) for 48 h and treated in the absence or presence of p-CA for 48 h. THP-1 macrophages were treated with combined ox-LDL (20 μg/mL) and LPS (500 ng/mL) for 24 h. The 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2H-tetrazolium bromide assays detected cell viability. Oil red O staining allowed us to observe lipid accumulation. Western blotting and quantitative polymerase chain reactions quantified corresponding proteins and mRNA. RESULTS: Ox-LDL and LPS for 24 h enhanced the lipid accumulation using Oil red O in treated foam cells. By contrast, p-CA treatment inhibited lipid accumulation. p-CA significantly upregulated cholesterol efflux-related genes such as ATP binding cassette transporter A1, liver-X-receptor α and peroxisome proliferator-activated receptor gamma expression. Moreover, p-CA decreased lipid accumulation-related gene such as lectin-like oxidized low-density lipoprotein receptor-1, cluster of differentiation 36 and scavenger receptor class A1 expression. Combined ox-LDL and LPS increased nuclear factor-κB (NFκB), cyclooxygenase-2 (COX-2) and pro-inflammatory (tumor necrosis factor-α [TNF-α] and interleukin [IL]-6) activation and expression compared with untreated. p-CA suppressed this increased expression of NF-κB and COX-2, TNF-α and IL-6. CONCLUSION p-CA may play a vital role in atherosclerosis inhibition and protective effects by suppressing lipid accumulation and foam cell creation by increasing cholesterol efflux and can be potential agents for preventing atherosclerosis.

BACKGROUND/OBJECTIVES: Atherosclerosis is a primary cause of cardiovascular disease associated with inflammation and lipid metabolism disorders. The accumulation of cholesterol-containing macrophage foam cells characterizes the early stages. The p-coumaric acid (p-CA) contained in vegetables may have various physiological activities. The inhibitory effect of p-CA on foam cell creation in THP-1 macrophages needs clarification. In this study, we explored the impact of p-CA on foam cells by co-treatment with oxidized lowdensity lipoprotein (ox-LDL) and lipopolysaccharides (LPS), mimicking the development of atherosclerosis in vitro and studied the regulation of its underlying mechanisms.MATERIALS/METHODS: THP-1 cells differentiated by phorbol 12-myristate 13-acetate (1 μM) for 48 h and treated in the absence or presence of p-CA for 48 h. THP-1 macrophages were treated with combined ox-LDL (20 μg/mL) and LPS (500 ng/mL) for 24 h. The 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2H-tetrazolium bromide assays detected cell viability. Oil red O staining allowed us to observe lipid accumulation. Western blotting and quantitative polymerase chain reactions quantified corresponding proteins and mRNA. RESULTS: Ox-LDL and LPS for 24 h enhanced the lipid accumulation using Oil red O in treated foam cells. By contrast, p-CA treatment inhibited lipid accumulation. p-CA significantly upregulated cholesterol efflux-related genes such as ATP binding cassette transporter A1, liver-X-receptor α and peroxisome proliferator-activated receptor gamma expression. Moreover, p-CA decreased lipid accumulation-related gene such as lectin-like oxidized low-density lipoprotein receptor-1, cluster of differentiation 36 and scavenger receptor class A1 expression. Combined ox-LDL and LPS increased nuclear factor-κB (NFκB), cyclooxygenase-2 (COX-2) and pro-inflammatory (tumor necrosis factor-α [TNF-α] and interleukin [IL]-6) activation and expression compared with untreated. p-CA suppressed this increased expression of NF-κB and COX-2, TNF-α and IL-6. CONCLUSION p-CA may play a vital role in atherosclerosis inhibition and protective effects by suppressing lipid accumulation and foam cell creation by increasing cholesterol efflux and can be potential agents for preventing atherosclerosis.

BACKGROUND/OBJECTIVES: Atherosclerosis is a primary cause of cardiovascular disease associated with inflammation and lipid metabolism disorders. The accumulation of cholesterol-containing macrophage foam cells characterizes the early stages. The p-coumaric acid (p-CA) contained in vegetables may have various physiological activities. The inhibitory effect of p-CA on foam cell creation in THP-1 macrophages needs clarification. In this study, we explored the impact of p-CA on foam cells by co-treatment with oxidized lowdensity lipoprotein (ox-LDL) and lipopolysaccharides (LPS), mimicking the development of atherosclerosis in vitro and studied the regulation of its underlying mechanisms.MATERIALS/METHODS: THP-1 cells differentiated by phorbol 12-myristate 13-acetate (1 μM) for 48 h and treated in the absence or presence of p-CA for 48 h. THP-1 macrophages were treated with combined ox-LDL (20 μg/mL) and LPS (500 ng/mL) for 24 h. The 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2H-tetrazolium bromide assays detected cell viability. Oil red O staining allowed us to observe lipid accumulation. Western blotting and quantitative polymerase chain reactions quantified corresponding proteins and mRNA. RESULTS: Ox-LDL and LPS for 24 h enhanced the lipid accumulation using Oil red O in treated foam cells. By contrast, p-CA treatment inhibited lipid accumulation. p-CA significantly upregulated cholesterol efflux-related genes such as ATP binding cassette transporter A1, liver-X-receptor α and peroxisome proliferator-activated receptor gamma expression. Moreover, p-CA decreased lipid accumulation-related gene such as lectin-like oxidized low-density lipoprotein receptor-1, cluster of differentiation 36 and scavenger receptor class A1 expression. Combined ox-LDL and LPS increased nuclear factor-κB (NFκB), cyclooxygenase-2 (COX-2) and pro-inflammatory (tumor necrosis factor-α [TNF-α] and interleukin [IL]-6) activation and expression compared with untreated. p-CA suppressed this increased expression of NF-κB and COX-2, TNF-α and IL-6. CONCLUSION p-CA may play a vital role in atherosclerosis inhibition and protective effects by suppressing lipid accumulation and foam cell creation by increasing cholesterol efflux and can be potential agents for preventing atherosclerosis.

BACKGROUND/OBJECTIVES: Atherosclerosis is a primary cause of cardiovascular disease associated with inflammation and lipid metabolism disorders. The accumulation of cholesterol-containing macrophage foam cells characterizes the early stages. The p-coumaric acid (p-CA) contained in vegetables may have various physiological activities. The inhibitory effect of p-CA on foam cell creation in THP-1 macrophages needs clarification. In this study, we explored the impact of p-CA on foam cells by co-treatment with oxidized lowdensity lipoprotein (ox-LDL) and lipopolysaccharides (LPS), mimicking the development of atherosclerosis in vitro and studied the regulation of its underlying mechanisms.MATERIALS/METHODS: THP-1 cells differentiated by phorbol 12-myristate 13-acetate (1 μM) for 48 h and treated in the absence or presence of p-CA for 48 h. THP-1 macrophages were treated with combined ox-LDL (20 μg/mL) and LPS (500 ng/mL) for 24 h. The 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2H-tetrazolium bromide assays detected cell viability. Oil red O staining allowed us to observe lipid accumulation. Western blotting and quantitative polymerase chain reactions quantified corresponding proteins and mRNA. RESULTS: Ox-LDL and LPS for 24 h enhanced the lipid accumulation using Oil red O in treated foam cells. By contrast, p-CA treatment inhibited lipid accumulation. p-CA significantly upregulated cholesterol efflux-related genes such as ATP binding cassette transporter A1, liver-X-receptor α and peroxisome proliferator-activated receptor gamma expression. Moreover, p-CA decreased lipid accumulation-related gene such as lectin-like oxidized low-density lipoprotein receptor-1, cluster of differentiation 36 and scavenger receptor class A1 expression. Combined ox-LDL and LPS increased nuclear factor-κB (NFκB), cyclooxygenase-2 (COX-2) and pro-inflammatory (tumor necrosis factor-α [TNF-α] and interleukin [IL]-6) activation and expression compared with untreated. p-CA suppressed this increased expression of NF-κB and COX-2, TNF-α and IL-6. CONCLUSION p-CA may play a vital role in atherosclerosis inhibition and protective effects by suppressing lipid accumulation and foam cell creation by increasing cholesterol efflux and can be potential agents for preventing atherosclerosis.

BACKGROUND/OBJECTIVES: Atherosclerosis is a primary cause of cardiovascular disease associated with inflammation and lipid metabolism disorders. The accumulation of cholesterol-containing macrophage foam cells characterizes the early stages. The p-coumaric acid (p-CA) contained in vegetables may have various physiological activities. The inhibitory effect of p-CA on foam cell creation in THP-1 macrophages needs clarification. In this study, we explored the impact of p-CA on foam cells by co-treatment with oxidized lowdensity lipoprotein (ox-LDL) and lipopolysaccharides (LPS), mimicking the development of atherosclerosis in vitro and studied the regulation of its underlying mechanisms.MATERIALS/METHODS: THP-1 cells differentiated by phorbol 12-myristate 13-acetate (1 μM) for 48 h and treated in the absence or presence of p-CA for 48 h. THP-1 macrophages were treated with combined ox-LDL (20 μg/mL) and LPS (500 ng/mL) for 24 h. The 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2H-tetrazolium bromide assays detected cell viability. Oil red O staining allowed us to observe lipid accumulation. Western blotting and quantitative polymerase chain reactions quantified corresponding proteins and mRNA. RESULTS: Ox-LDL and LPS for 24 h enhanced the lipid accumulation using Oil red O in treated foam cells. By contrast, p-CA treatment inhibited lipid accumulation. p-CA significantly upregulated cholesterol efflux-related genes such as ATP binding cassette transporter A1, liver-X-receptor α and peroxisome proliferator-activated receptor gamma expression. Moreover, p-CA decreased lipid accumulation-related gene such as lectin-like oxidized low-density lipoprotein receptor-1, cluster of differentiation 36 and scavenger receptor class A1 expression. Combined ox-LDL and LPS increased nuclear factor-κB (NFκB), cyclooxygenase-2 (COX-2) and pro-inflammatory (tumor necrosis factor-α [TNF-α] and interleukin [IL]-6) activation and expression compared with untreated. p-CA suppressed this increased expression of NF-κB and COX-2, TNF-α and IL-6. CONCLUSION p-CA may play a vital role in atherosclerosis inhibition and protective effects by suppressing lipid accumulation and foam cell creation by increasing cholesterol efflux and can be potential agents for preventing atherosclerosis.

We report a rare case of gastric adenocarcinoma with enteroblastic differentiation (GAED) that was treated with endoscopic submucosal dissection followed by additional distal gastrectomy with lymph node dissection. A 67-year-old man underwent endoscopic submucosal dissection for a gastric lesion, which was diagnosed as GAED with submucosal and lymphatic invasion. Histologically, GAED is characterized by a tubulopapillary growth pattern and clear cells that resemble those of the primitive fetal gut. Immunohistochemically, GAED variably expresses oncofetal proteins such as glypican-3, alpha-fetoprotein, and spalt-like transcription factor 4. Despite negative margins, additional gastrectomy with lymph node dissection was performed due to submucosal and lymphatic invasion.No residual tumor or metastasis was detected, and the patient remained disease-free for 2 years before dying from causes unrelated to GAED. Given its aggressive nature, frequent lymphovascular invasion, and high metastatic potential, clinicians should recognize the histopathological diagnosis of this rare tumor and its propensity for aggressiveness.

Signet-ring cell carcinoma (SRCC) is a rare tumor that most commonly occurs in the stomach. Duodenal SRCCs are extremely uncommon and account for approximately 1% of duodenal adenocarcinomas. Although Brunner’s gland hyperplasia (BGH) is a benign duodenal condition, studies have reported several cases of adenocarcinoma originating in an area of BGH. We report a rare case of early-stage SRCC originating in an area of BGH that was successfully treated using endoscopic mucosal resection. Based on the mucin phenotype observed in this case, it is reasonable to conclude that SRCC originated from gastric metaplasia in the area of BGH. Although BGH is a benign condition, careful evaluation is warranted for early detection of combined neoplasms.

Background: There is insufficient data on the benefits of empiric antibiotic combinations for hospital-acquired pneumonia (HAP). We aimed to investigate whether empiric antipseudomonal combination therapy with fluoroquinolones decreases mortality in patients with HAP. Methods: This multicenter, retrospective cohort study included adult patients admitted to 16 tertiary and general hospitals in Korea between January 1 and December 31, 2019.Patients with risk factors for combination therapy were divided into anti-pseudomonal non-carbapenem β-lactam monotherapy and fluoroquinolone combination therapy groups.Primary outcome was 30-day mortality. Propensity score matching (PSM) was used to reduce selection bias. Results: In total, 631 patients with HAP were enrolled. Monotherapy was prescribed in 54.7% (n = 345) of the patients, and combination therapy was prescribed in 45.3% (n = 286).There was no significant difference in 30-day mortality between the two groups (16.8% vs.18.2%, P = 0.729) or even after the PSM (17.5% vs. 18.2%, P = 0.913). After the PSM, adjusted hazard ratio for 30-day mortality from the combination therapy was 1.646 (95% confidence interval, 0.782–3.461; P = 0.189) in the Cox proportional hazards model. Moreover, there was no significant difference in the appropriateness of initial empiric antibiotics between the two groups (55.0% vs. 56.8%, P = 0.898). The proportion of multidrug-resistant (MDR) pathogens was high in both groups. Conclusion Empiric anti-pseudomonal fluoroquinolone combination therapy showed no survival benefit compared to β-lactam monotherapy in patients with HAP. Caution is needed regarding the routine combination of fluoroquinolones in the empiric treatment of HAP patients with a high risk of MDR.

BACKGROUND/OBJECTIVES: Oxidative stress is a fundamental neurodegenerative disease trigger that damages and decimates nerve cells. Neurodegenerative diseases are chronic central nervous system disorders that progress and result from neuronal degradation and loss. Recent studies have extensively focused on neurodegenerative disease treatment and prevention using dietary compounds. Heseperetin is an aglycone hesperidin form with various physiological activities, such as anti-inflammation, antioxidant, and antitumor. However, few studies have considered hesperetin’s neuroprotective effects and mechanisms; thus, our study investigated this in hydrogen peroxide ( H 2 O 2 )-treated SH-SY5Y cells.MATERIALS/METHODS: SH-SY5Y cells were treated with H 2 O 2 (400 µM) in hesperetin absence or presence (10–40 µM) for 24 h. Three-(4,5-Dimethyl-2-thiazolyl)-2,5-diphenyl-2H-tetrazolium bromide assays detected cell viability, and 4′,6-diamidino-2-phenylindole staining allowed us to observe nuclear morphology changes such as chromatin condensation and apoptotic nuclei. Reactive oxygen species (ROS) detection assays measured intracellular ROS production; Griess reaction assays assessed nitric oxide (NO) production. Western blotting and quantitative polymerase chain reactions quantified corresponding mRNA and proteins. RESULTS: Subsequent experiments utilized various non-toxic hesperetin concentrations, establishing that hesperetin notably decreased intracellular ROS and NO production in H 2 O 2 -treated SH-SY5Y cells (P < 0.05). Furthermore, hesperetin inhibited H 2 O 2 -induced inflammation-related gene expression, including interluekin-6, tumor necrosis factor-α, and nuclear factor kappa B (NF-κB) p65 activation. In addition, hesperetin inhibited NFκB translocation into H 2 O 2 -treated SH-SY5Y cell nuclei and suppressed mitogen-activated protein kinase protein expression, an essential apoptotic cell death regulator. Various apoptosis hallmarks, including shrinkage and nuclear condensation in H 2 O 2 -treated cells, were suppressed dose-dependently. Additionally, hesperetin treatment down-regulated Bax/ Bcl-2 expression ratios and activated AMP-activated protein kinase-mammalian target of rapamycin autophagy pathways. CONCLUSION These results substantiate that hesperetin activates autophagy and inhibits apoptosis and inflammation. Hesperetin is a potentially potent dietary agent that reduces neurodegenerative disease onset, progression, and prevention