Gomisin A Suppresses Colorectal Lung Metastasis by Inducing AMPK/p38-Mediated Apoptosis and Decreasing Metastatic Abilities of Colorectal Cancer Cells

Gomisin A (G.A) is a dietary lignan compound from Schisandra chinensis. In this study, the effect of G.A on the proliferation and metastasis of colorectal cancer (CRC) cells was investigated using several CRC cell lines and a lung metastasis mouse model. Both oral and intraperitoneal administration of G.A (50 mg/kg) inhibited lung metastasis of CT26 cells. Various concentrations of G.A were incubated with CRC cell lines and their viability was determined using a cell counting kit-8 assay. G.A significantly decreased the viability of various CRC cell lines, whereas it did not change the proliferation of normal colon cells. G.A induced G0/G1 phase arrest and apoptosis of CT26 and HT29 cells by regulating cyclin D1/cyclin-dependent kinase 4 (CDK4) expression and apoptotic proteins such as caspases and B-cell lymphoma-2 (Bcl-2) family proteins, respectively. G.A-induced apoptosis was mediated by AMPK/p38 activation in CRC cells. A non-cytotoxic concentration of G.A inhibited epithelial–mesenchymal transition of CRC cells by modulating E-cadherin and N-cadherin expression levels. Moreover, the migration and invasion of CRC cells were reduced by G.A treatment. Especially, G.A decreased matrix metalloproteinase (MMP)-2 and MMP-9 expressions and activities. G.A ameliorated lung metastasis of CRC cells by decreasing cell survival and metastatic abilities of CRC cells. Thus, G.A might be a potential novel therapeutic agent for metastatic CRC

Association between serum osteoprotegerin level and renal prognosis in nondialysis patients with chronic kidney disease in the Korean Cohort Study for Outcomes in Patients with Chronic Kidney Disease (the KNOW-CKD Study)

Background Osteoprotegerin is an important regulator of bone metabolism and vascular calcification. The association between serum osteoprotegerin level and chronic kidney disease (CKD) progression has not been elucidated. We investigated the prognostic value of serum osteoprotegerin levels in nondialysis CKD patients. Methods We analyzed 2,082 patients enrolled in the Korean Cohort Study for Outcomes in Patients with CKD between 2011 and 2016. Patients were divided into quartiles by their serum osteoprotegerin levels. The primary outcome was the occurrence of ≥1 of the following: dialysis initiation, kidney transplantation, a two-fold increase in serum creatinine level from baseline, or a 50% decrease in the estimated glomerular filtration rate (eGFR). Cox proportional hazard regression models were used to investigate the prognostic value of the serum osteoprotegerin level to CKD progression. Results The median follow-up period was 48.9 months, and 641 patients (30.8%) experienced the primary outcome. The hazard ratio of serum osteoprotegerin for renal progression in the full extended Cox proportional hazard model was 1.064 (95% confidence interval, 1.041–1.088). Subgroup analyses by age, presence of diabetes, and eGFR showed significant results consistent with the overall analysis results. Conclusion Serum osteoprotegerin level is independently associated with renal prognosis and could have prognostic importance in CKD progression

Lenzimycins A and B, metabolites with antibacterial properties from Brevibacillus sp. associated with the dung beetle Onthophagus lenzii

Symbiotic microorganisms associated with insects can produce a wide array of metabolic products, which provide an opportunity for the discovery of useful natural products. Selective isolation of bacterial strains associated with the dung beetle, Onthophagus lenzii, identified two strains, of which the antibiotic-producing Brevibacillus sp. PTH23 inhibited the growth of Bacillus sp. CCARM 9248, which is most closely related to the well-known entomopathogen, Bacillus thuringiensis. A comprehensive chemical investigation based on antibiotic activity discovered two new antibiotics, named lenzimycins A and B (1-2), which inhibited growth of Bacillus sp. CCARM 9248. The 1H and 13C NMR, MS, MS/MS, and IR analyses elucidated the structures of 1 and 2, which comprised a novel combination of fatty acid (12-methyltetradecanoic acid), glycerol, sulfate, and N-methyl ethanolamine. Furthermore, the acid hydrolysis of 1 revealed the absolute configuration of 12-methyltetradecanoic acid as 12S by comparing its optical rotation value with authentic (R)- and (S)-12-methyltetradecanoic acid. In addition to inhibition of Bacillus sp. CCARM 9248, lenzimycins A and B were found to inhibit the growth of some human pathogenic bacteria, including Enterococcus faecium and certain strains of Enterococcus faecalis. Furthermore, the present study elucidated that lenzimycins A and B activated a reporter system designed to detect the bacterial cell envelope stress, thereby indicating an activity against the integrity of the bacterial cell wall

Gender Differences in Diagnostic Values of Visceral Fat Area and Waist Circumference for Predicting Metabolic Syndrome in Koreans

Abdominal fat accumulation is known to be strongly implicated in development of metabolic syndrome (MetS). We examined diagnostic values of obesity-related parameters in 95 men and 185 women, and we determined optimal cutoff values of visceral fat area (VFA) and waist circumference (WC) for predicting the presence of multiple non-adipose components of MetS. Receiver operating characteristic (ROC) curve analysis revealed that VFA was the best indicator of MetS. WC and VFA exhibited similar diagnostic values for men and postmenopausal women, whereas WC was inferior to VFA for premenopausal women (area under ROC curve of VFA and WC was 0.76 and 0.52, respectively; P < 0.001). Optimal cutoff points of VFA and WC for predicting MetS were 136 cm2 and 89 cm in men and 95 cm2 and 82 cm in women, respectively. Subjects with VFA and WC above these cutoff values exhibited increased insulin resistance and increased carotid intima-media thickness. In conclusion, WC has a diagnostic value similar to VFA for predicting MetS in men and postmenopausal women, but not in premenopausal women. Further studies are necessary to develop a simple clinical parameter that reflects visceral fat in premenopausal women

Hypocomplementemia (C3) as an Independent Predictor for Children with Acute Post-streptococcal Glomerulonephritis: A Long-Term Observation

OBJECTIVE: The aim of this study was to examine the altering patterns in clinical characteristics and severity of acute post-streptococcal glomerulonephritis (APSGN) in children. PATIENTS AND METHODS: We analyzed the medical records of 119 children who were diagnosed with APSGN from 1987 to 2018, retrospectively. The patients were divided into two groups: Group I (n=72, before 1998) and Group II (n=47, after 1998). Clinical, radiologic, and laboratory findings were compared between the two groups. RESULTS: The clinical manifestations, including vomiting (20.8% vs. 4.3%, p=0.014), oliguria (40.3% vs. 19.1%, p=0.016), and generalized edema (86.1% vs. 63.8%, p=0.005), were statistically less frequent since 1998. Pulmonary edema on chest X-ray (22.7% vs. 4.4%, p=0.014) was less frequent in Group II than in Group I. The level of BUN (23.3±19.3 vs. 18.8±11.2, p=0.009) was lower in Group II than in Group I, while that of creatinine was not significantly different between the two groups. C3 level was an independent factor for predicting the development of edema (odds ratio [OR]: 1.034, 95% CI: 1.010-1.060, p=0.006) and acute nephritic symptoms (≥2) (OR: 0.974, 95% CI: 0.952-0996, p=0.020). It was also negatively correlated with an increasing number of acute nephritic symptoms, including oliguria and edema, in patients with APSGN (R=−0.182, p=0.048). CONCLUSIONS: This study demonstrated that APSGN had favorable clinical manifestations and severity over the past 30 years. The monitoring of C3 levels can be used to assess the disease severity and risk of complications, including edema and oliguria, which are decreasing in South Korean children

Reversible Cerebral Vasoconstriction Syndrome: A Comprehensive Systematic Review

OBJECTIVE: We aimed to analyze clinical characteristics, treatment patterns, and prognosis of patients with reversible cerebral vasoconstriction syndrome (RCVS). MATERIALS AND METHODS: Two investigators independently searched PubMed and EMBASE, and 191 cases were included in this study. Information regarding demographics, triggering factors, brain imaging findings, treatment modalities, recurrence, and clinical outcome was collected. RESULTS: The mean age of the patients was 39.9 years, and 155 (81.2%) were female. The most common triggering factor for RCVS was an exposure to vasoactive substances (41.4%), followed by pregnancy/postpartum (20.9%), and sexual intercourse (10.5%). Multifocal stenosis (84.0%) and beading shape (82.4%) were the leading abnormal findings on angiography, while cerebral ischemic lesions (47.6%) and cerebral hemorrhage (mainly subarachnoid hemorrhage) (35.1%) were the main findings on brain computed tomography (CT)/magnetic resonance imaging (MRI). Calcium channel blockers (nimodipine/verapamil) were the most commonly used medications (44.5%) in the treatment of RCVS. Multivariate analysis identified that RCVS was precipitated by trauma/surgery/procedure (hazard ratio (HR): 3.29, 95% confidence interval (CI) (1.21-8.88), p=0.019), and presence of aphasia/neglect/apraxia during the acute phase of the disease (HR: 3.83, 95% CI (1.33-11.05), p=0.013) were found to be the two independent risk factors for residual neurological deficit after RCVS. CONCLUSIONS: In our systematic review, vasoactive substances were the most frequent triggers for RCVS, which was most commonly accompanied by angiographic findings of multifocal stenotic lesions. Patients with RCVS precipitated by trauma or surgical procedures and those with focal cortical deficits had a higher risk of residual neurological deficits, and these patients should closely be monitored