Randomized controlled trial testing weight loss and abdominal obesity outcomes of moxibustion

Background

The purpose of this study was to investigate the efficacy of moxibustion therapy on weight loss, waist circumference and waist-to-hip ratio in young adult females. An experimental design, 51 Asian females were enrolled. Inclusion criteria included females with ages between 21 and 25 years-old and waist circumference?≥?80 cm, and the exclusion criteria included intolerance to moxibustion therapy and current illness. Two groups were formed, and the subjects in the experimental group received moxibustion sessions lasting 20 min and an educational video program for 30 min; however, participants in the control group received only the educational program every other week for 8 weeks. Dependent variable measurements (e.g., body weight, waist circumference and waist-to-hip ratio) were collected at baseline and follow-up for 8 weeks.

Results

Average body weight of the treatment group decreased significantly from ??1.478 kg (p?<?0.0001), while the average body weight in the control group did not decrease significantly ??0.038 kg (p?=?0.7197). Also, individuals in the moxibustion experimental group showed significant reductions (p?<?0.0001) in both waist circumference and waist-to-hip ratio.

Conclusion

Positive effects on anthropometry can be achieved by moxibustion intervention in conjunction with a weight loss education program. Especially waist circumference and waist-to-hip ratio had more clinically significant and more pronounced for health reasons Future studies can focus on the functional assessment of biomarkers associated with the immune system and relevant mechanisms of action.

     

Hepatic Circadian-Clock System Altered by Insulin Resistance,Diabetes and Insulin Sensitizer in Mice

Circadian rhythms are intrinsic rhythms that are coordinated with the rotation of the Earth and are also generated by a set of circadian-clock genes at the intracellular level. Growing evidence suggests a strong link between circadian rhythms and energy metabolism; however, the fundamental mechanisms remain unclear. In the present study, neonatal streptozotocin (STZ)-treated mice were used to model the molecular and physiological progress from insulin resistance to diabetes. Two-day-old male C57BL/6 mice received a single injection of STZ and were tested for non-obese, hyperglycemic and hyperinsulinemic conditions in the early stage, insulin resistance in the middle stage, and diabetes in the late stage. Gene expression levels of the hepatic circadian-clock system were examined by real-time quantitative PCR. Most of the components of the hepatic circadian-clock gene expression system, such as the mRNAs of Bmal1 (brain and muscle Arnt-like protein-1), Per2 (period 2) and Cry1 (cryptochrome 1), were elevated, and circadian patterns were retained in the early and middle stages of insulin-resistant conditions. The insulin sensitizer, rosiglitazone, returns the physiological and molecular changes associated with the diabetic phenotype to normal levels through peroxisome proliferator-activated receptor γ (PPARγ) rather than PPARα. Early and chronic treatment with rosiglitazone has been shown to be effective to counter the diabetic condition. Over time, this effect acts to attenuate the increased gene expression levels of the hepatic circadian-clock system and delay the severity of diabetic conditions. Together, these results support an essential role for the hepatic circadian-clock system in the coordinated regulation and/or response of metabolic pathways.     

Leukocyte Mitochondrial DNA Copy Number Is Associated with Chronic Obstructive Pulmonary Disease

Background

Oxidative stress is known to be involved in the pathogenesis of chronic obstructive pulmonary disease (COPD). Evidence suggests that leukocytes mitochondria DNA (mtDNA) is susceptible to undergo mutations, insertions, or depletion in response to reactive oxidative stress (ROS). We hypothesize that mtDNA copy number is associated with the development of COPD.

Methodology/Principal Findings

Relative mtDNA copy number was measured by a quantitative real-time PCR assay using DNA extracted from peripheral leukocytes. MtDNA copy number of peripheral leukocytes in the COPD group (n = 86) is significantly decreased compared with non-smoker group (n = 77) (250.3± 21.5 VS. 464.2± 49.9, P<0.001). MtDNA copy number in the COPD group was less than that in the healthy smoking group, but P value nearly achieved significance (250.3± 21.5 VS. 404.0± 76.7, P = 0.08) MtDNA copy number has no significance with age, gender, body mass index, current smoking, and pack-years in COPD group, healthy smoker group and no smoker group, respectively. Serum glutathione level in the COPD group is significantly decreased compared with healthy smoker and non-smoker groups (4.5± 1.3 VS. 6.2± 1.9 and 4.5± 1.3 VS. 7.1±1.1 mU/mL; P<0.001 respectively). Pearson correlation test shows a significant liner correlation between mtDNA copy number and serum glutathione level (R = 0.2, P = 0.009).

Conclusions/Significance

COPD is associated with decreased leukocyte mtDNA copy number and serum glutathione. COPD is a regulatory disorder of leukocytes mitochondria. However, further studies are needed to determine the real mechanisms about the gene and the function of mitochondria.     

Functional complementation of the adenovirus E1B 19-kilodalton protein with Bcl-2 in the inhibition of apoptosis in infected cells.

Expression of the adenovirus E1A oncogene induces apoptosis which impedes both the transformation of primary rodent cells and productive adenovirus infection of human cells. Coexpression of E1A with the E1B 19,000-molecular-weight protein (19K protein) or the Bcl-2 protein, both of which have antiapoptotic activity, is necessary for efficient transformation. Induction of apoptosis by E1A in rodent cells is mediated by the p53 tumor suppressor gene, and both the E1B 19K protein and the Bcl-2 protein can overcome this p53-dependent apoptosis. The functional similarity between Bcl-2 and the E1B 19K protein suggested that they may act by similar mechanisms and that Bcl-2 may complement the requirement for E1B 19K expression during productive infection. Infection of human HeLa cells with E1B 19K loss-of-function mutant adenovirus produces apoptosis characterized by enhanced cytopathic effects (cyt phenotype) and degradation of host cell chromosomal DNA and viral DNA (deg phenotype). Failure to inhibit apoptosis results in premature host cell death, which impairs virus yield. HeLa cells express extremely low levels of p53 because of expression of human papillomavirus E6 protein. Levels of p53 were substantially increased by E1A expression during adenovirus infection. Therefore, E1A may induce apoptosis by overriding the E6-induced degradation of p53 and promoting p53 accumulation. Stable Bcl-2 overexpression in HeLa cells infected with the E1B 19K- mutant adenovirus blocked the induction of the cyt and deg phenotypes. Expression of Bcl-2 in HeLa cells also conferred resistance to apoptosis mediated by tumor necrosis factor alpha and Fas antigen, which is also an established function of the E1B 19K protein. A comparison of the amino acid sequences of Bcl-2 family members and that of the E1B 19K protein indicated that there was limited amino acid sequence homology between the central conserved domains of E1B 19K and Bcl-2. This domain of the E1B 19K protein is important in transformation and regulation of apoptosis, as determined by mutational analysis. The limited sequence homology and functional equivalency provided further evidence that the Bcl-2 and E1B 19K proteins may possess related mechanisms of action and that the E1B 19K protein may be the adenovirus equivalent of the cellular Bcl-2 protein.     

5-hydroxy-2-(4-hydroxy-3-methoxyphenyl)-3,7-dimethoxy-4H-chromen-4-one (MSF-2) suppresses fMLP-mediated respiratory burst in human neutrophils by inhibiting phosphatidylinositol 3-kinase activity

Respiratory burst mediates crucial bactericidal mechanism in neutrophils. However, undesirable respiratory burst leads to pathological inflammation and tissue damage. This study investigates the effect and the underlying mechanism of 5-hydroxy-2-(4-hydroxy-3-methoxyphenyl)-3,7-dimethoxy-4H-chromen-4-one (MSF-2), a lignan extracted from the fruit of Melicope Semecarprifolia, on fMLP-induced respiratory burst in human neutrophils and suggests a possible therapeutic approach to ameliorate disease associated with neutrophil hyperactivation. MSF-2 inhibited fMLP-induced neutrophil superoxide anion production, cathepsin G release and migration in human neutrophils isolated from healthy volunteers, reflecting inhibition of phosphatidylinositol 3-kinase (PI3K) activation. Specifically, PI3K/AKT activation results in migration, degranulation and superoxide anion production in neutrophils. MSF-2 suppresses PI3K activation and phosphatidylinositol (3,4,5)-trisphosphate (PIP3) production, and consequently inhibits downstream activation of PDK1 and AKT. Further, PI3K also stimulates respiratory burst via PLC-dependent elevation of intracellular calcium. MSF-2 reduces fMLP-mediated PLCγ2 activation and intracellular calcium accumulation notably through extracellular calcium influx in a PI3K and PLC-dependent manner. However, MSF-2 is not a competitive or allosteric antagonist of fMLP. Additionally, in an in vivo study, MSF-2 prevents fMLP-induced neutrophil infiltration and inflammation in mice. In conclusion, MSF-2 opposes fMLP-mediated neutrophil activation and inflammation by inhibiting PI3K activation and subsequent activation of AKT and PLCγ2.     

Innate immune responses of human tracheal epithelium to Pseudomonas aeruginosa flagellin, TNF-alpha, and IL-1beta

We measured innate immune responses by primary human tracheal epithelial (HTE) cells grown as confluent, pseudostratified layers during exposure to inflammatory activators on apical vs. basolateral surfaces. Apical Pseudomonas aeruginosa strain PAK (but not flagellin mutant PAK·fliC), flagellin, and flagellin + PAK·fliC activated NF-B and IL-8 expression and secretion. In contrast, HTE cells were insensitive to LPS compared to flagellin. Flagellin activated NF-B in columnar but not basal cells. IL-1 + TNF- elicited responses similar to those of flagellin. Basolateral flagellin or IL-1 + TNF- caused 1.5- to 4-fold larger responses, consistent with the fact that NF-B activation occurred in both columnar and basal cells. MyD88 (toll receptor-associated adapter), IL-1 receptor (IL1R)1, and TNF- receptor (TNFR)1 were expressed in columnar and basal cells. ZO-1 was localized to tight junctions of columnar cells but not to basal cells. We infer the following. 1) Flagellin is necessary and sufficient to trigger inflammatory responses in columnar cells during accumulation of P. aeruginosa in the airway surface liquid (ASL); columnar cells express toll-like receptor 5 and MyD88, often associated with flagellin-activated cell signaling. 2) IL-1 + TNF- in the ASL also activate columnar cells, and these cells also express IL1R1 and TNFR1. 3) Apical flagellin, IL-1, and TNF- do not activate basal cells because tight junctions between columnar cells prevent access from the apical surface to the basal cells. 4) Exposure of basolateral surfaces to inflammatory activators elicits larger responses because both columnar and basal cells are activated, likely because both cell types express receptors for flagellin, IL-1, and TNF-. toll-like receptor; nuclear factor-B; interleukin-8; tumor necrosis factor; interleukin-1     

A legionellosis case due to contaminated spa water and confirmed by genomic identification in Taiwan

Tracing the source of a legionellosis (LG) case revealed that the Legionella pneumophila (LP) strain isolated from patient's sputum shared the same serogroup (SG) and PFGE-type with 4 LP strains obtained from a spa center. With a high LP-contamination rate (81.2%, 13/16) in all of its 16 basins, this spa center was also found to have a multi-genotypic distribution among its 13 LP isolates, which can be categorized into 5 PFGE-types. Despite such a serious contamination in the spa center, which usually had ca. 100 visitors per day, this male patient, bearing LG-risk factors of long-term heavy smoking and alcoholism, was the only case identifiable after an active investigation. To explore the possible reason for this sporadic infection, all 5 PFGE-types of LP isolated were assayed for their presence of two important virulent genes (lvh and rtx A) and were identified as either less-virulent (lvh (+) , rtx A(+)) or non-virulent (lvh (-), rtx A (-)) types. The strong virulent type (lvh (+), rtx A (+)) usually seen in clinical strains elsewhere was not found here. Moreover, the LG-causative type in this infection was the only one to be classified as the less-virulent type, with the presence of lvh gene indicating its relatively more virulent potential than other 4 PFGE-types. Accordingly, mutual interaction between LP's virulent potential and patient's health-status was suggested to be the force directing the opportunistic infection of this sporadic case. This is the first spa-associated infection caused by SG 2 of LP.     

Embryonic and regenerating Xenopus retinal fibers are intrinsically different

Growth and guidance behavior of Xenopus embryonic (ER) (optic vesicle stage 25/26) and regenerating retinal fibers (stage 47/50 newly regenerating NR, and actively regenerating RR, respectively) have been studied in vitro on a variety of substrates in serum-free media. RR retinas receive a prior conditioning lesion 12-14 days before explantation while NR retinas are explanted immediately after axotomy. The substrates include plastic (UN), polylysine (PL), polyornithine (PO), laminin (LM), fibronectin (FN), and collagen type I (CO). Two kinds of experimental situations were tested, one in which substrates were derivatized to plastic as a planar surface, while the second involved the addition of a substrate as a soluble supplement to dishes derivatized with PL. A neurite growth index (NGI), based on density of neurite outgrowth and axon lengths, is determined for each fiber type on all substrates. Embryonic and regenerating fibers are phenotypically different fiber types; each displays a specific "substrate preference profile" (SPP), reflecting differential growth on each substrate. ER neurites grow equally well on all planar substrates, including plastic, but do not grow on CO (SPP, LM = FN = PL = PO = UN greater than CO). Both NR and RR neurites show distinct substrate preferences, but RR neurites grow more vigorously (SPP, LM greater than CO greater than PL = PO greater than FN). In media supplemented with LM, FN or CO, the SPPs showed little change but the neurite bundle patterns were qualitatively different. Only regenerating neurites display clockwise growth in laminin (LM) and fibronectin (FN)-supplemented media. Under no conditions do embryonic fibers exhibit this pattern which suggests that embryonic and regenerating retinal fibers also differ in cytoskeletal organization. Evidence of intrinsic growth differences in vitro suggest that embryonic and regenerating retinal fibers may not respond to identical guidance cues during in vivo development and regeneration of retinotectal connections.