Morus alba and active compound oxyresveratrol exert anti-inflammatory activity via inhibition of leukocyte migration involving MEK/ERK signaling

Background: Morus alba has long been used in traditional Chinese medicine to treat inflammatory diseases;however, the scientific basis for such usage and the mechanism of action are not well understood. This studyinvestigated the action of M. alba on leukocyte migration, one key step in inflammation.Methods: Gas chromatography-mass spectrometry (GC-MS) and cluster analyses of supercritical CO2 extractsof three Morus species were performed for chemotaxonomy-aided plant authentication. Phytochemistry andCXCR4-mediated chemotaxis assays were used to characterize the chemical and biological properties of M. albaand its active compound, oxyresveratrol. fluorescence-activated cell sorting (FACS) and Western blot analyses wereconducted to determine the mode of action of oxyresveratrol.Results: Chemotaxonomy was used to help authenticate M. alba. Chemotaxis-based isolation identifiedoxyresveratrol as an active component in M. alba. Phytochemical and chemotaxis assays showed that the crudeextract, ethyl acetate fraction and oxyresveratrol from M. alba suppressed cell migration of Jurkat T cells in responseto SDF-1. Mechanistic study indicated that oxyresveratrol diminished CXCR4-mediated T-cell migration via inhibitionof the MEK/ERK signaling cascade.Conclusions: A combination of GC-MS and cluster analysis techniques are applicable for authentication of theMorus species. Anti-inflammatory benefits of M. alba and its active compound, oxyresveratrol, may involve theinhibition of CXCR-4-mediated chemotaxis and MEK/ERK pathway in T and other immune cells

Catenarin Prevents Type 1 Diabetes in Nonobese Diabetic Mice via Inhibition of Leukocyte Migration Involving the MEK6/p38 and MEK7/JNK Pathways

Inflammation contributes to leukocyte migration, termed insulitis, and β-cell loss in type 1 diabetes (T1D). Naturally occurring anthraquinones are claimed as anti-inflammatory compounds; however, their actions are not clear. This study aimed to investigate the effect and mechanism of catenarin on the inflammatory disease, T1D. Catenarin and/or its anthraquinone analogs dose-dependently suppressed C-X-C chemokine receptor type 4 (CXCR4)- and C-C chemokine receptor type 5 (CCR5)-implicated chemotaxis in leukocytes. Catenarin, the most potent anthraquinone tested in the study, prevented T1D in nonobese diabetic mice. Mechanistic study showed that catenarin did not act on the expression of CCR5 and CXCR4. On the contrary, catenarin inhibited CCR5- and CXCR4-mediated chemotaxis via the reduction of the phosphorylation of mitogen-activated protein kinases (p38 and JNK) and their upstream kinases (MKK6 and MKK7), and calcium mobilization. Overall, the data demonstrate the preventive effect and molecular mechanism of action of catenarin on T1D, suggesting its novel use as a prophylactic agent in T1D

Combined Phytochemistry and Chemotaxis Assays for Identification and Mechanistic Analysis of Anti-Inflammatory Phytochemicals in Fallopia japonica

Plants provide a rich source of lead compounds for a variety of diseases. A novel approach combining phytochemistry and chemotaxis assays was developed and used to identify and study the mechanisms of action of the active compounds in F. japonica, a medicinal herb traditionally used to treat inflammation. Based on a bioactivity-guided purification strategy, two anthranoids, emodin and physcion, were identified from F. japonica. Spectroscopic techniques were used to characterize its crude extract, fractions and phytochemicals. The crude extract, chloroform fraction, and anthranoids of F. japonica significantly inhibited CXCR4-mediated chemotaxis. Mechanistic studies showed that emodin and physcion inhibited chemotaxis via inactivating the MEK/ERK pathway. Moreover, the crude extract and emodin could prevent or treat type 1 diabetes in non-obese diabetic (NOD) mice. This study illustrates the applicability of a combinational approach for the study of anti-inflammatory medicine and shows the potential of F. japonica and its anthranoids for anti-inflammatory therapy

Congenital Chylothorax in a Late Preterm Infant and Successful Treatment With Octreotide

Chylothorax is defined as abnormal accumulation of lymphatic fluid in the pleural space and is a rare condition in neonates. Chylothorax causes respiratory and nutritional problems and a significant mortality rate. Octreotide is a long-acting somatostatin analog that can reduce lymphatic fluid production and has been used as a new strategy in the treatment of chylothorax. Here, we report a premature baby with severe bilateral pleural effusion diagnosed by prenatal ultrasound and subsequently confirmed to be congenital chylothorax after birth. This newborn baby was initially treated with bilateral chest tube insertion to relieve severe respiratory distress. However, the chylothorax recurred after a medium-chain-triglyceride-enriched formula was initiated. The accumulation of chylothorax diminished after the administration of octreotide. Therefore, octreotide may allow the patient to avoid invasive procedures, such as reinsertion of chest tubes or surgery

Association of Umbilical Cord Plasma Acid-labile Subunit of the Insulin-like Growth Factor Ternary Complex with Anthropometry in Term Newborns

Birth size can affect neonatal morbidity and mortality. The insulin-like growth factor (IGF) system is the most important endocrine factor influencing fetal growth. In the circulation, IGFs (mostly IGF-I) are bound to IGF-binding protein 3 (IGFBP-3) and an acid-labile subunit (ALS) to form a ternary complex. The ALS protects IGFs from decay and facilitates their endocrine activity. However, the function of ALS in fetal growth has not yet been fully determined. Methods: Venous umbilical plasma samples were obtained from 98 term neonates and analyzed using enzyme-linked immunosorbent assays. The ALS, IGF-I, and IGFBP-3 umbilical cord plasma levels were analyzed for their association with anthropometric measurements of the neonates. Results: The ALS, IGF-I, and IGFBP-3 cord plasma levels were positively correlated with birth weight (r = 0.42, p < 0.001; r = 0.43, p < 0.001; and r = 0.27, p < 0.01, respectively) and placental weight (r = 0.37, p < 0.001; r = 0.31, p < 0.01; and r = 0.30, p < 0.01, respectively). In addition, the ALS cord plasma levels were also positively correlated with head circumference (r = 0.29, p < 0.01). Multiple linear regression analyses showed that both ALS and IGF-I cord plasma levels were independent predictive variables for birth weight (p < 0.01 and p < 0.005, respectively). The ALS cord plasma levels were the only independent predictive variables, however, for head circumference and placental weight (p < 0.01 and p < 0.05, respectively). Conclusion: The ALS umbilical cord plasma levels are one important factor, in addition to IGF-I, in the IGF system for predicting birth anthropometry, at least for near-term gestation. Our results suggest that the influence of ALS on the IGF system may develop prior to birth and affect fetal growth

Pay for performance program reduces treatment needed diabetic retinopathy - a nationwide matched cohort study in Taiwan

Abstract Background Pay-for-Performance programs have shown improvement in indicators monitoring adequacy and target achievement in diabetic care. However, less is known regarding the impact of this program on the occurrence and long-term effects of diabetic retinopathy. The objective of this study was to determine the effect of pay-for-performance program on the development of treatment needed for diabetic retinopathy in type 2 diabetes patients. Methods We conducted a nationwide retrospective cohort study with a matching design using the Taiwan National Health Insurance Research Database from 2000 to 2012. The outcome was defined as the treatment needed diabetic retinopathy. We matched Pay-for-Performance and non-Pay-for-Performance groups for age, gender, year diabetes was diagnosed and study enrollment, and duration of follow-up. Results A total of 9311 patients entered the study cohort, of whom 2157 were registered in the Pay-for-Performance group and 7154 matched in the non-Pay-for-Performance group. The incidence of treatment needed diabetic retinopathy was not significantly different in two groups. However, the incidence of treatment needed diabetic retinopathy was significantly different if restricted the non-Pay-for-Performance group who had at least 1 eye examination or optical coherence tomography within 1 year (adjusted hazard ratio, 0.78; 95% confidence interval, 0.64–0.94). Conclusions Pay-for-Performance is valuable in preventing the development of treatment needed diabetic retinopathy, which could be attributed to the routine eye examination required in the Pay-for-Performance program. We could improve our diabetic care by promoting eye health education and patient awareness on the importance of regular examinations

Association of Cord Plasma Leptin With Birth Size in Term Newborns

Leptin is secreted from adipose tissue and plays an important role in obesity. Recent studies have shown that the relationship between leptin and body fat mass may have ethnic differences. The purpose of our study was to investigate the relationship between venous umbilical cord plasma leptin and anthropometric markers in term healthy Taiwanese newborns. Methods: Umbilical venous plasma samples were obtained from 98 term neonates (48 males and 50 females) and leptin levels were analyzed by enzyme-linked immunosorbent assay. Results: Umbilical cord plasma levels of leptin were significantly higher in the female neonates than in males (p < 0.001). The large-for-gestational age and appropriate- for-gestational age newborns had significantly higher leptin cord plasma levels than the small-for-gestational age newborns (p < 0.01 and p < 0.05, respectively). In both male and female neonates, umbilical leptin levels showed significant positive correlations with birth weight and birth length. Multiple linear regression analysis revealed that birth weight was the only significant predictor of umbilical cord plasma leptin levels in both male and female neonates. However, the slopes of the regressions between leptin and birth weight in male and female neonates were not different. Conclusion: In Taiwanese healthy term neonates, leptin umbilical cord plasma levels are associated with sex and birth weight of the neonate. The relationship between leptin and birth weight may differ among different ethnic groups. These findings imply that the relationship between leptin and body fat mass may develop early in life

Chinese handwriting performance in preterm children in grade 2.

BACKGROUND:First graders born prematurely perform poorly on handwriting speed and legibility. However, whether there are specific legibility factors in which preterm children demonstrate difficulty remains unknown. In addition, handwriting performance beyond the first grade and the influence of sex on handwriting performance in preterm children are still unclear. We aimed to investigate the influence of prematurity and sex on multiple dimensions of handwriting in grade two and to identify the contributors to performance. METHODS:Sixty-three preterm (34 boys and 29 girls) and 67 full-term (27 boys and 40 girls) peers in grade two were included. Class teachers were asked to complete the Chinese Handwriting Evaluation Form. A subgroup of 39 preterm children received assessments on intelligence, visual perception, tactile and kinesthetic sensation, and fine motor skills. Their inattention behavior was rated using a maternal self-report with a behavioral scale. RESULTS:Boys born prematurely exhibited poorer performance in the speed dimension than full-term boys (p = 0.008), whereas there was comparable performance in the two groups of girls (p = 0.221). In the dimensions related to legibility, preterm boys (32.4%) had a higher percentage of children with difficulty in the construction dimension than the other groups (preterm girls: 6.9%, full-term boys: 7.4%, full-term girls: 5.0%). However, no group difference was found in the dimensions of accuracy and directionality. Of the sensory-perceptual-motor factors, attention was the most significant predictor of accuracy in performance (p = 0.046) and speed dimensions (p = 0.001) in preterm children. CONCLUSIONS:Boys appear to be vulnerable to the adverse impacts of preterm birth in terms of performance in the dimensions of speed and construction in grade two. Based on the significant contribution of attention to handwriting performance in preterm children, assessment and intervention in the area of attention is strongly suggested for preterm children with handwriting problems