Broussonetia papyrifera Root Bark Extract Exhibits Anti-inflammatory Effects on Adipose Tissue and Improves Insulin Sensitivity Potentially Via AMPK Activation

The chronic low-grade inflammation in adipose tissue plays a causal role in obesity-induced insulin resistance and its associated pathophysiological consequences. In this study, we investigated the effects of extracts of Broussonetia papyrifera root bark (PRE) and its bioactive components on inflammation and insulin sensitivity. PRE inhibited TNF-alpha-induced NF-kappa B transcriptional activity in the NF-kappa B luciferase assay and pro-inflammatory genes' expression by blocking phosphorylation of I kappa B and NF-kappa B in 3T3-L1 adipocytes, which were mediated by activating AMPK. Ten-week-high fat diet (HFD)-fed C57BL6 male mice treated with PRE had improved glucose intolerance and decreased inflammation in adipose tissue, as indicated by reductions in NF-kappa B phosphorylation and pro-inflammatory genes' expression. Furthermore, PRE activated AMP-activated protein kinase (AMPK) and reduced lipogenic genes' expression in both adipose tissue and liver. Finally, we identified broussoflavonol B (BF) and kazinol J (KJ) as bioactive constituents to suppress pro-inflammatory responses via activating AMPK in 3T3-L1 adipocytes. Taken together, these results indicate the therapeutic potential of PRE, especially BF or KJ, in metabolic diseases such as obesity and type 2 diabetes

VisAlign: Dataset for Measuring the Degree of Alignment between AI and Humans in Visual Perception

AI alignment refers to models acting towards human-intended goals, preferences, or ethical principles. Given that most large-scale deep learning models act as black boxes and cannot be manually controlled, analyzing the similarity between models and humans can be a proxy measure for ensuring AI safety. In this paper, we focus on the models' visual perception alignment with humans, further referred to as AI-human visual alignment. Specifically, we propose a new dataset for measuring AI-human visual alignment in terms of image classification, a fundamental task in machine perception. In order to evaluate AI-human visual alignment, a dataset should encompass samples with various scenarios that may arise in the real world and have gold human perception labels. Our dataset consists of three groups of samples, namely Must-Act (i.e., Must-Classify), Must-Abstain, and Uncertain, based on the quantity and clarity of visual information in an image and further divided into eight categories. All samples have a gold human perception label; even Uncertain (severely blurry) sample labels were obtained via crowd-sourcing. The validity of our dataset is verified by sampling theory, statistical theories related to survey design, and experts in the related fields. Using our dataset, we analyze the visual alignment and reliability of five popular visual perception models and seven abstention methods. Our code and data is available at \url{https://github.com/jiyounglee-0523/VisAlign}

Associations of patient-generated subjective global assessment (PG-SGA) and NUTRISCORE with survival in gastric cancer patients: timing matters, a retrospective cohort study

Background The timing of nutritional assessment may be important to treat cancer patients and predict their prognosis. This study examined whether Patient-Generated Subjective Global Assessment (PG-SGA) and NUTRISCORE scores were associated with survival among gastric cancer patients who underwent surgery and chemotherapy and whether the timing of the assessment after surgery mattered. Methods A total of 952 gastric cancer patients (622 men and 330 women) were included in this retrospective cohort study. The PG-SGA and NUTRISCORE scores were calculated at 1 month (n = 952), 2 months (n = 657), and 3 months (n = 294) after surgery. Cox proportional hazards model was used to calculate the hazard ratios (HRs) and 95% confidence intervals (CIs). Results The PG-SGA scores assessed at 1 month after gastrectomy were not associated with survival. However, high PG-SGA scores at 2 months after gastrectomy (median = 65 days) were associated with an increased risk of mortality; the HR (95% CI) was 2.26 (1.22–4.21) for 9–11 vs. ≤ 5 of PG-SGA scores. When we included patients who received all three consecutive consultations, HR (95% CI) was 2.56 (1.02–6.42) for ≥ 9 (malnutrition) vs. ≤ 8 of PG-SGA scores assessed at 3 months after surgery (median days = 98 days). Likewise, high NUTRISCORE scores assessed at the 3-month follow-up were associated with higher mortality; the HR (95% CI) was 3.84 (1.18–12.55) for ≥ 7 vs. ≤ 4 of NUTRISCORE scores. Conclusion Malnutrition assessed with the PG-SGA and NUTRISCORE at 2 to 3 months after gastrectomy was associated with poor survival among gastric cancer patients. Our findings suggest that the timing of the nutritional evaluation may be important in identifying and treating malnutrition related to gastric cancer prognosis

Quercetin, the active phenolic component in kiwifruit, prevents hydrogen peroxide-induced inhibition of gap-junction intercellular communication

We evaluated the effects of the two main kiwifruit cultivars (gold kiwifruit (GOK) and green kiwifruit (GRK)) and their active phenolic compound, quercetin, on H2O2-induced inhibition of gap-junction intercellular communication (GJIC) in WB-F344 rat liver epithelial cells. We found that both GOK and GRK protect WB-F344 cells from H2O2-induced inhibition of GJIC. The extracellular signal-regulated protein kinase 1/2 (ERK1/2)-connexin 43 (Cx43) signalling pathway is crucial for the regulation of GJIC, and both GOK and GRK blocked the H2O2-induced phosphorylation of Cx43 and ERK1/2 in WB-F344 cells. Quercetin alone attenuated the H2O2-mediated ERK1/2-Cx43 signalling pathway and consequently reversed H2O2-mediated inhibition of GJIC in WB-F344 cells. A free radical-scavenging assay using 1,1-diphenyl-2-picrylhydrazyl showed that the scavenging activity of quercetin was higher than that of a synthetic antioxidant, butylated hydroxytoluene, per mol, suggesting that the chemopreventive effect of quercetin on H2O2-mediated inhibition of ERK1/2-Cx43 signalling and GJIC may be mediated through its free radical-scavenging activity. Since the carcinogenicity of reactive oxygen species such as H2O2 is attributable to the inhibition of GJIC, GOK, GRK and quercetin may have chemopreventive potential by preventing the inhibition of GJI

Verminoside from Pseudolysimachion rotundum var. subintegrum sensitizes cisplatin-resistant cancer cells and suppresses metastatic growth of human breast cancer

Breast cancer is one of the most common cancers in women and is associated with a high mortality rate. The majority of deaths resulting from breast cancer are attributable to metastatic growth; in addition, chemoresistance is a major concern in the treatment of patients with breast cancer. However, limited drugs are available for the treatment of metastatic breast cancer. In this study, the chemoadjuvant effects of a methanolic extract from the leaves of Pseudolysimachion rotundum var. subintegrum (NC13) and an active component isolated from the plant, verminoside (Vms), were evaluated. Furthermore, their potent anti-metastatic activities were validated in vitro and in vivo in animal models. The anti-metastatic and chemosensitizing activities of NC13 and Vms on cisplatin treatment were found to be partly mediated by suppression of the epithelial-mesenchymal transition of cancer cells. Collectively, our results implied that NC13 and its bioactive component Vms could be developed as effective chemoadjuvants in combination with conventional therapeutics

Longitudinal association between adiposity changes and lung function deterioration

Background The longitudinal relationship between adiposity and lung function is controversial. We aimed to investigate the long-term association between adiposity changes and lung function in a middle-aged general Asian population. Methods In total, 5011 participants (average age, 54years; 45% men) were enrolled from a community-based prospective cohort. During the follow-up period (median 8years), both spirometry and bio-electrical impedance analysis were performed biannually. Individual slopes of the fat mass index (FMI; fat mass divided by the square of height in meters) and waist-to-hip ratio (WHR) were calculated using linear regression analysis. Multivariate linear mixed regression analysis was used to determine the long-term association between adiposity changes and lung function. Results The FMI was inversely associated with forced vital capacity (FVC) (estimated: − 31.8mL in men, − 27.8mL in women) and forced expiratory volume in 1s (FEV1) (estimated: − 38.2mL in men, − 17.8mL in women) after adjusting for baseline age, height, residential area, smoking exposure (pack-years, men only), initial adiposity indices, and baseline lung function. The WHR was also inversely associated with FVC (estimated = − 1242.2mL) and FEV1 (estimated = − 849.8mL) in men. The WHR-increased group showed a more rapid decline in lung function than the WHR-decreased group in both the fat-gain and fat-loss groups. Conclusion Adiposity was associated with the long-term impairment of lung function. Central obesity was the main driver of lung function impairment in the middle-aged general Asian population, regardless of fat mass changes

Laparoscopic treatment of paraprostatic cyst in two dogs – complete resection, and partial resection with omentalization: a case report

Two intact male dogs were evaluated for symptoms, including hematuria, prostatomegaly, anuria, lethargy, and abdominal mass. Presurgical evaluations, including complete physical examinations, blood examinations, abdominal radiography with contrast (only in Case 2), ultrasonography, and computed tomography and magnetic resonance imaging (only in Case 1), were performed. A paraprostatic cyst was diagnosed initially, and laparoscopic exploration and surgery were performed. Complete resection was performed in case 1, whereas partial resection with omentalization was performed in case 2. Histopathological examination of the tissue samples confirmed the presence of paraprostatic pseudocysts in both cases, with no evidence of an epithelial lining. These two cases represent the first documented instances of laparoscopic treatment for extraparenchymal prostatic cysts. The laparoscopic treatment proved feasible even in the case of a giant cyst causing anuria (Case 2). Paraprostatic cysts should be considered a potential differential diagnosis for abnormal urination accompanied by an abdominal mass, and long-term postoperative follow-up is necessary

Tonicity-responsive enhancer-binding protein promotes hepatocellular carcinogenesis, recurrence and metastasis

Objectives: Hepatocellular carcinoma (HCC) is a common cancer with high rate of recurrence and mortality. Diverse aetiological agents and wide heterogeneity in individual tumours impede effective and personalised treatment. Tonicity-responsive enhancer-binding protein (TonEBP) is a transcriptional cofactor for the expression of proinflammatory genes. Although inflammation is intimately associated with the pathogenesis of HCC, the role of TonEBP is unknown. We aimed to identify function of TonEBP in HCC. Design: Tumours with surrounding hepatic tissues were obtained from 296 patients with HCC who received completion resection. TonEBP expression was analysed by quantitative reverse transcription-quantitative real-time PCR (RT-PCR) and immunohfistochemical analyses of tissue microarrays. Mice with TonEBP haplodeficiency, and hepatocyte-specific and myeloid-specific TonEBP deletion were used along with HCC and hepatocyte cell lines. Results: TonEBP expression is higher in tumours than in adjacent non-tumour tissues in 92.6% of patients with HCC regardless of aetiology associated. The TonEBP expression in tumours and adjacent non-tumour tissues predicts recurrence, metastasis and death in multivariate analyses. TonEBP drives the expression of cyclo-oxygenase-2 (COX-2) by stimulating the promoter. In mouse models of HCC, three common sites of TonEBP action in response to diverse aetiological agents leading to tumourigenesis and tumour growth were found: cell injury and inflammation, induction by oxidative stress and stimulation of the COX-2 promoter. Conclusions: TonEBP is a key component of the common pathway in tumourigenesis and tumour progression of HCC in response to diverse aetiological insults. TonEBP is involved in multiple steps along the pathway, rendering it an attractive therapeutic target as well as a prognostic biomarker

The clinicopathologic characteristics and prognostic significance of triple-negativity in node-negative breast cancer

Background: Triple-negative (TN) breast cancer, which is defined as being negative for the estrogen receptor (ER), the progesterone receptor (PR), and the human epidermal growth factor receptor 2 (HER-2), represents a subset of breast cancer with different biologic behaviour. We investigated the clinicopathologic characteristics and prognostic indicators of lymph node-negative TN breast cancer. Methods: Medical records were reviewed from patients with node-negative breast cancer who underwent curative surgery at Seoul National University Hospital between Jan. 2000 and Jun. 2003. Clinicopathologic variables and clinical outcomes were evaluated. Results: Among 683 patients included, 136 had TN breast cancer and 529 had non-TN breast cancer. TN breast cancer correlated with younger age (< 35 y, p = 0.003), and higher histologic and nuclear grade (p < 0.001). It also correlated with a molecular profile associated with biological aggressiveness: negative for bcl-2 expression (p < 0.001), positive for the epidermal growth factor receptor (p = 0.003), and a high level of p53 (p < 0.001) and Ki67 expression (p < 0.00). The relapse rates during the follow-up period (median, 56.8 months) were 14.7% for TN breast cancer and 6.6% for non-TN breast cancer (p = 0.004). Relapse free survival (RFS) was significantly shorter among patients with TN breast cancer compared with those with non-TN breast cancer (4-year RFS rate 85.5% vs. 94.2%, respectively; p = 0.001). On multivariate analysis, young age, close resection margin, and triple-negativity were independent predictors of shorter RFS. Conclusion: TN breast cancer had higher relapse rate and more aggressive clinicopathologic characteristics than non-TN in node-negative breast cancer. Thus, TN breast cancer should be integrated into the risk factor analysis for node-negative breast cancer