Cadmium (Cd), one of well-known highly toxic environmental and industrial pollutants, causes a number of adverse health effects and diseases in humans. The growing epidemiological studies have suggested a possible link between Cd exposure and diabetes mellitus (DM). However, the toxicological effects and underlying mechanisms of Cd-induced pancreatic β-cell injury are still unknown. In this study, we found that Cd significantly decreased cell viability, and increased sub-G1 hypodiploid cells and annexin V-Cy3 binding in pancreatic β-cell-derived RIN-m5F cells. Cd also increased intracellular reactive oxygen species (ROS) generation and malondialdehyde (MDA) production and induced mitochondrial dysfunction (the loss of mitochondrial membrane potential (MMP) and the increase of cytosolic cytochrome c release), the decreased Bcl-2 expression, increased p53 expression, poly (ADP-ribose) polymerase (PARP) cleavage, and caspase cascades, which accompanied with intracellular Cd accumulation. Pretreatment with the antioxidant N-acetylcysteine (NAC) effectively reversed these Cd-induced events. Furthermore, exposure to Cd induced the phosphorylations of c-jun N-terminal kinases (JNK), extracellular signal-regulated kinases (ERK)1/2, and p38-mitogen-activated protein kinase (MAPK), which was prevented by NAC. Additionally, the specific JNK inhibitor SP600125 or JNK-specific small interference RNA (si-RNA) transfection suppressed Cd-induced β-cell apoptosis and related signals, but not ERK1/2 and p38-MAPK inhibitors (PD98059 and SB203580) did not. However, the JNK inhibitor or JNK-specific si-RNA did not suppress ROS generation in Cd-treated cells. These results indicate that Cd induces pancreatic β-cell death via an oxidative stress downstream-mediated JNK activation-triggered mitochondria-regulated apoptotic pathway.

Background: Nowadays, the individual differences are emphasized in personalized medicine. Traditional Chinese Medicine (TCM) which prescribes tailored treatment based on each patient’s different body constitution may provide new strategy to break the bottleneck of modern medicine (MM). Therefore, to integrate TCM into MM, an objective, reliable and rigorous diagnostic tool is necessary for the assessment of TCM constitution of each individual. This study aimed to develop a provisional version of the Yin-Xu Constitution Questionnaire (BCQ–), because evaluating the level of individual’s Yin deficiency (Yin-Xu) by his manifestations is frequently involved in TCM clinical trials. Methods: The provisional version of BCQ– was developed using a step-by-step approach: 1) to form the research team and select a panel of 26 experts who had both MM and TCM educational background and professional training for Delphi method; 2) to generate questionnaire items from literature review and Delphi process, refine these items to be colloquially acceptable, and evaluate their face and content validities by Delphi process again; 3) to evaluate the difficulty of answering these questions by a pilot study with 81 participants whose age ranged from 20 to 60 years. Results: After 2 rounds of Delphi process, 22 colloquially appropriate questions were established and answered without difficulty by the 81 participants. Conclusions: This provisional version of BCQ– appeared to have considerable face and content validities and may be the basis to develop an advanced Yin-Xu questionnaire. The reliability and validity of BCQ– were further tested in the second part of the study.

Summary Background Findings from studies of the relation between early antibiotic use and subsequent asthma have been inconsistent, which may be attributable to methodologic issues. Objective Our objective was to assess the impact of confounding by indication on the relation of early antibiotic use to childhood asthma through age 5 in a non-selected birth cohort (n = 424). Methods Oral antibiotic use was assessed by frequent nurse interviews in the first 9 months of life. Physician-diagnosed active asthma and eczema were assessed by questionnaire at 1, 2, 3, and 5 years, and were considered as ever asthma or ever eczema if positive at any age. Allergen-specific IgE was assessed in plasma at 1, 2, 3, and 5 years. Confounding by indication was investigated by considering the relation of asthma to antibiotic use while controlling for the number of illness visits to a physician in early life. Results There was no statistically significant relation of early antibiotic use with physician-diagnosed eczema or allergen-specific IgE. A dose–response relation was evident for antibiotic use with ever asthma (odds ratio [OR] = 1.5, P = 0.047). Ever asthma also increased significantly with the number of illness visits to a physician (P<0.001). After adjustment for number of illness visits, antibiotic use showed no relation with asthma. Conclusions The relation of asthma to antibiotics in this cohort appears to be an artefact of the strong relation of number of physician visits for illness with both antibiotic use and risk for asthma.

Nurses could be trained in acupressure and meridian massage techniques to provide more effective level of clinical care for premature infants.

Inflammation is a serious health issue worldwide that induces many diseases, such as inflammatory bowel disease (IBD), sepsis, acute pancreatitis and lung injury. Thus, there is a great deal of interest in new methods of limiting inflammation. In this study, we investigated the leaves of Nelumbo nucifera Gaertn, an aquatic perennial plant cultivated in eastern Asia and India, in anti-inflammatory pharmacological effects in the murine macrophage cell line RAW264.7. Results showed that lipopolysaccharide (LPS) increased the protein expression of inducible nitric oxide synthase (iNOS) and COX-2, as well as the mRNA expression and level of IL-6 and TNF-α, while NNE significantly reduced these effects of LPS. LPS also induced phospho-JNK protein expression. The JNK-specific inhibitor SP600125 decreased the proteins expression of phospho-JNK, iNOS, COX-2, and the mRNAs expression and levels of IL-6 and TNF-α. Further, NNE reduced the protein expression of phospho-JNK. LPS was also found to promote the translocation of NF-κB from the cytosol to the nucleus and to decrease the expression of cytosolic IκB. NNE and SP600125 treatment recovered the LPS-induced expression of NF-κB and IκB. While phospho-ERK and phospho-p38 induced by LPS, could not be reversed by NNE. To further investigate the major components of NNE in anti-inflammatory effects, we determined the quercetin and catechin in inflammatory signals. Results showed that quercetin and catechin significantly decreased the proteins expression of iNOS, COX-2 and phospho-JNK. Besides, the mRNAs and levels of IL-6 and TNF-α also decreased by quercetin and catechin treatment in LPS-induced RAW264.7 cells. These results showed that NNE and its major components quercetin and catechin exhibit anti-inflammatory activities by inhibiting the JNK- and NF-κB-regulated pathways and could therefore be an useful anti-inflammatory agent.