Mechanism of action of probiotics

The modern diet doesn't provide the required amount of beneficial bacteria. Maintenance of a proper microbial ecology in the host is the main criteria to be met for a healthy growth. Probiotics are one such alternative that are supplemented to the host where by and large species of Lactobacillus, Bifidobacterium and Saccharomyces are considered as main probiotics. The field of probiotics has made stupendous strides though there is no major break through in the identification of their mechanism of action. They exert their activity primarily by strengthening the intestinal barrier and immunomodulation. The main objective of the study was to provide a deep insight into the effect of probiotics against the diseases, their applications and proposed mechanism of action

AMP-activated protein kinase inhibits NF-κB signaling and inflammation: impact on healthspan and lifespan

Adenosine monophosphate-activated protein kinase (AMPK) is a crucial regulator of energy metabolic homeostasis and thus a major survival factor in a variety of metabolic stresses and also in the aging process. Metabolic syndrome is associated with a low-grade, chronic inflammation, primarily in adipose tissue. A low-level of inflammation is also present in the aging process. There are emerging results indicating that AMPK signaling can inhibit the inflammatory responses induced by the nuclear factor-κB (NF-κB) system. The NF-κB subunits are not direct phosphorylation targets of AMPK, but the inhibition of NF-κB signaling is mediated by several downstream targets of AMPK, e.g., SIRT1, PGC-1α, p53, and Forkhead box O (FoxO) factors. AMPK signaling seems to enhance energy metabolism while it can repress inflammatory responses linked to chronic stress, e.g., in nutritional overload and during the aging process. AMPK can inhibit endoplasmic reticulum and oxidative stresses which are involved in metabolic disorders and the aging process. Interestingly, many target proteins of AMPK are so-called longevity factors, e.g., SIRT1, p53, and FoxOs, which not only can increase the stress resistance and extend the lifespan of many organisms but also inhibit the inflammatory responses. The activation capacity of AMPK declines in metabolic stress and with aging which could augment the metabolic diseases and accelerate the aging process. We will review the AMPK pathways involved in the inhibition of NF-κB signaling and suppression of inflammation. We also emphasize that the capacity of AMPK to repress inflammatory responses can have a significant impact on both healthspan and lifespan

Complete Genome Sequence and Comparative Analysis of the Fish Pathogen Lactococcus garvieae

Lactococcus garvieae causes fatal haemorrhagic septicaemia in fish such as yellowtail. The comparative analysis of genomes of a virulent strain Lg2 and a non-virulent strain ATCC 49156 of L. garvieae revealed that the two strains shared a high degree of sequence identity, but Lg2 had a 16.5-kb capsule gene cluster that is absent in ATCC 49156. The capsule gene cluster was composed of 15 genes, of which eight genes are highly conserved with those in exopolysaccharide biosynthesis gene cluster often found in Lactococcus lactis strains. Sequence analysis of the capsule gene cluster in the less virulent strain L. garvieae Lg2-S, Lg2-derived strain, showed that two conserved genes were disrupted by a single base pair deletion, respectively. These results strongly suggest that the capsule is crucial for virulence of Lg2. The capsule gene cluster of Lg2 may be a genomic island from several features such as the presence of insertion sequences flanked on both ends, different GC content from the chromosomal average, integration into the locus syntenic to other lactococcal genome sequences, and distribution in human gut microbiomes. The analysis also predicted other potential virulence factors such as haemolysin. The present study provides new insights into understanding of the virulence mechanisms of L. garvieae in fish

Biodiversity and structure of spider communities along a metal pollution gradient

The objective of the study was to determine whether long-term metal pollution affects communities of epigeal spiders (Aranea), studied at three taxonomic levels: species, genera, and families. Biodiversity was defined by three indices: the Hierarchical Richness Index (HRI), Margalef index (DM) and Pielou evenness index (J). In different ways the indices describe taxa richness and the distribution of individuals among taxa. The dominance pattern of the communities was described with four measures: number of dominant species at a site, percentage of dominant species at a site, average dominant species abundance at a site, and the share of the most numerous species (Alopecosa cuneata) at a site. Spiders were collected along a metal pollution gradient in southern Poland, extending ca. 33 km from zinc and lead smelter to an uncontaminated area. The zinc concentration in soil was used as the pollution index.The study revealed a significant effect of metal pollution on spider biodiversity as described by HRI for species (p = 0.039), genera (p = 0.0041) and families (p = 0.0147), and by DM for genera (p = 0.0259) and families (p = 0.0028). HRI correlated negatively with pollution level, while DM correlated positively. This means that although broadly described HRI diversity decreased with increasing pollution level, species richness increased with increasing contamination. Mesophilic meadows were generally richer. Pielou (J) did not show any significant correlations. There were a few evidences for the intermediate disturbance hypothesis: certain indices reached their highest values at moderate pollution levels rather than at the cleanest or most polluted sites

Curcumin-induced HDAC inhibition and attenuation of medulloblastoma growth in vitro and in vivo

<p>Abstract</p> <p>Background</p> <p>Medulloblastoma is the most common brain tumor in children, and its prognosis is worse than for many other common pediatric cancers. Survivors undergoing treatment suffer from serious therapy-related side effects. Thus, it is imperative to identify safer, effective treatments for medulloblastoma. In this study we evaluated the anti-cancer potential of curcumin in medulloblastoma by testing its ability to induce apoptosis and inhibit tumor growth <it>in vitro </it>and <it>in vivo </it>using established medulloblastoma models.</p> <p>Methods</p> <p>Using cultured medulloblastoma cells, tumor xenografts, and the Smo/Smo transgenic medulloblastoma mouse model, the antitumor effects of curcumin were tested <it>in vitro </it>and <it>in vivo</it>.</p> <p>Results</p> <p>Curcumin induced apoptosis and cell cycle arrest at the G2/M phase in medulloblastoma cells. These effects were accompanied by reduced histone deacetylase (HDAC) 4 expression and activity and increased tubulin acetylation, ultimately leading to mitotic catastrophe. In <it>in vivo </it>medulloblastoma xenografts, curcumin reduced tumor growth and significantly increased survival in the Smo/Smo transgenic medulloblastoma mouse model.</p> <p>Conclusions</p> <p>The <it>in vitro </it>and <it>in vivo </it>data suggest that curcumin has the potential to be developed as a therapeutic agent for medulloblastoma.</p

Oridonin induces apoptosis and senescence in colorectal cancer cells by increasing histone hyperacetylation and regulation of p16, p21, p27 and c-myc

<p>Abstract</p> <p>Background</p> <p>Oridonin, a tetracycline diterpenoid compound, has the potential antitumor activities. Here, we evaluate the antitumor activity and action mechanisms of oridonin in colorectal cancer.</p> <p>Methods</p> <p>Effects of oridonin on cell proliferation were determined by using a CCK-8 Kit. Cell cycle distribution was determined by flow cytometry. Apoptosis was examined by analyzing subdiploid population and terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling assay. Senescent cells were determined by senescence-associated β-galactosidase activity analysis. Semi-quantitative RT-PCR was used to examine the changes of mRNA of p16, p21, p27 and c-myc. The concomitant changes of protein expression were analyzed with Western blot. Expression of AcH3 and AcH4 were examined by immunofluorescence staining and Western blots. Effects of oridonin on colony formation of SW1116 were examined by Soft Agar assay. The in vivo efficacy of oridonin was detected using a xenograft colorectal cancer model in nude mice.</p> <p>Results</p> <p>Oridonin induced potent growth inhibition, cell cycle arrest, apoptosis, senescence and colony-forming inhibition in three colorectal cancer cell lines in a dose-dependent manner in vitro. Daily i.p. injection of oridonin (6.25, 12.5 or 25 mg/kg) for 28 days significantly inhibited the growth of SW1116 s.c. xenografts in BABL/C nude mice. With western blot and reverse transcription-PCR, we further showed that the antitumor activities of oridonin correlated with induction of histone (H3 and H4) hyperacetylation, activation of p21, p27 and p16, and suppression of c-myc expression.</p> <p>Conclusion</p> <p>Oridonin possesses potent in vitro and in vivo anti-colorectal cancer activities that correlated with induction of histone hyperacetylation and regulation of pathways critical for maintaining growth inhibition and cell cycle arrest. Therefore, oridonin may represent a novel therapeutic option in colorectal cancer treatment.</p

Does working memory training have to be adaptive?

This study tested the common assumption that, to be most effective, working memory (WM) training should be adaptive (i.e., task difficulty is adjusted to individual performance). Indirect evidence for this assumption stems from studies comparing adaptive training to a condition in which tasks are practiced on the easiest level of difficulty only [cf. Klingberg (Trends Cogn Sci 14:317-324, 2010)], thereby, however, confounding adaptivity and exposure to varying task difficulty. For a more direct test of this hypothesis, we randomly assigned 130 young adults to one of the three WM training procedures (adaptive, randomized, or self-selected change in training task difficulty) or to an active control group. Despite large performance increases in the trained WM tasks, we observed neither transfer to untrained structurally dissimilar WM tasks nor far transfer to reasoning. Surprisingly, neither training nor transfer effects were modulated by training procedure, indicating that exposure to varying levels of task difficulty is sufficient for inducing training gains

Staging investigations for oesophageal cancer: a meta-analysis

The aim of the study was to compare the diagnostic performance of endoscopic ultrasonography (EUS), computed tomography (CT), and 18F-fluoro-2-deoxy-D-glucose positron emission tomography (FDG-PET) in staging of oesophageal cancer. PubMed was searched to identify English-language articles published before January 2006 and reporting on diagnostic performance of EUS, CT, and/or FDG-PET in oesophageal cancer patients. Articles were included if absolute numbers of true-positive, false-negative, false-positive, and true-negative test results were available or derivable for regional, celiac, and abdominal lymph node metastases and/or distant metastases. Sensitivities and specificities were pooled using a random effects model. Summary receiver operating characteristic analysis was performed to study potential effects of study and patient characteristics. Random effects pooled sensitivities of EUS, CT, and FDG-PET for regional lymph node metastases were 0.80 (95% confidence interval 0.75–0.84), 0.50 (0.41–0.60), and 0.57 (0.43–0.70), respectively, and specificities were 0.70 (0.65–0.75), 0.83 (0.77–0.89), and 0.85 (0.76–0.95), respectively. Diagnostic performance did not differ significantly across these tests. For detection of celiac lymph node metastases by EUS, sensitivity and specificity were 0.85 (0.72–0.99) and 0.96 (0.92–1.00), respectively. For abdominal lymph node metastases by CT, these values were 0.42 (0.29–0.54) and 0.93 (0.86–1.00), respectively. For distant metastases, sensitivity and specificity were 0.71 (0.62–0.79) and 0.93 (0.89–0.97) for FDG-PET and 0.52 (0.33–0.71) and 0.91 (0.86–0.96) for CT, respectively. Diagnostic performance of FDG-PET for distant metastases was significantly higher than that of CT, which was not significantly affected by study and patient characteristics. The results suggest that EUS, CT, and FDG-PET each play a distinctive role in the detection of metastases in oesophageal cancer patients. For the detection of regional lymph node metastases, EUS is most sensitive, whereas CT and FDG-PET are more specific tests. For the evaluation of distant metastases, FDG-PET has probably a higher sensitivity than CT. Its combined use could however be of clinical value, with FDG-PET detecting possible metastases and CT confirming or excluding their presence and precisely determining the location(s)

Assessment of brain age in posttraumatic stress disorder: Findings from the ENIGMA PTSD and brain age working groups

BACKGROUND: Posttraumatic stress disorder (PTSD) is associated with markers of accelerated aging. Estimates of brain age, compared to chronological age, may clarify the effects of PTSD on the brain and may inform treatment approaches targeting the neurobiology of aging in the context of PTSD. METHOD: Adult subjects (N = 2229; 56.2% male) aged 18-69 years (mean = 35.6, SD = 11.0) from 21 ENIGMA-PGC PTSD sites underwent T1-weighted brain structural magnetic resonance imaging, and PTSD assessment (PTSD+, n = 884). Previously trained voxel-wise (brainageR) and region-of-interest (BARACUS and PHOTON) machine learning pipelines were compared in a subset of control subjects (n = 386). Linear mixed effects models were conducted in the full sample (those with and without PTSD) to examine the effect of PTSD on brain predicted age difference (brain PAD; brain age - chronological age) controlling for chronological age, sex, and scan site. RESULTS: BrainageR most accurately predicted brain age in a subset (n = 386) of controls (brainageR: ICC = 0.71, R = 0.72, MAE = 5.68; PHOTON: ICC = 0.61, R = 0.62, MAE = 6.37; BARACUS: ICC = 0.47, R = 0.64, MAE = 8.80). Using brainageR, a three-way interaction revealed that young males with PTSD exhibited higher brain PAD relative to male controls in young and old age groups; old males with PTSD exhibited lower brain PAD compared to male controls of all ages. DISCUSSION: Differential impact of PTSD on brain PAD in younger versus older males may indicate a critical window when PTSD impacts brain aging, followed by age-related brain changes that are consonant with individuals without PTSD. Future longitudinal research is warranted to understand how PTSD impacts brain aging across the lifespan