Chronic obstructive pulmonary disease (COPD) is a global disease characterised by chronic obstruction of lung airflow interfering with normal breathing. Although the microbiota of respiratory tract ...is established to be associated with COPD, the causality of gut microbiota in COPD development is not yet established. We aimed to address the connection between gut microbiota composition and lung COPD development, and characterise bacteria and their derived active components for COPD amelioration.
A murine cigarette smoking (CS)-based model of COPD and strategies evaluating causal effects of microbiota were performed. Gut microbiota structure was analysed, followed by isolation of target bacterium. Single cell RNA sequencing, together with sera metabolomics analyses were performed to identify host responsive molecules. Bacteria derived active component was isolated, followed by functional assays.
Gut microbiota composition significantly affects CS-induced COPD development, and faecal microbiota transplantation restores COPD pathogenesis. A commensal bacterium
was isolated and shown to ameliorate COPD. Reduction of intestinal inflammation and enhancement of cellular mitochondrial and ribosomal activities in colon, systematic restoration of aberrant host amino acids metabolism in sera, and inhibition of lung inflammations act as the important COPD ameliorative mechanisms. Besides, the lipopolysaccharide derived from
is anti-inflammatory, and significantly ameliorates COPD by acting as an antagonist of toll-like receptor 4 signalling pathway.
The gut microbiota-lung COPD axis was connected. A potentially benefial bacterial strain and its functional component may be developed and used as alternative agents for COPD prevention or treatment.
Colorectal cancer is one of the major causes of cancer-related mortality in both men and women worldwide. This review focuses on preventing the initiation and promotion of neoplastic growth in ...colorectal cancer, particularly with natural dietary compounds. Chemoprevention is defined as the use of natural dietary compounds and/or synthetic substances that can delay, prevent, or even reverse the development of adenomas, as well as the progression from adenoma to carcinoma. The molecular mechanisms of their chemopreventive action are associated with the modulation of signaling cascades, gene expressions involved in the regulation of cell proliferation, differentiation, and apoptosis and the suppression of chronic inflammation, metastasis, and angiogenesis. Here, we summarize the currently known targets and signaling pathways whereby natural dietary compounds interfere with the development of colorectal cancer, and thus providing evidence for these substances in colonic cancer chemopreventive action.
Scope
SlimTrym® is a formulated product composed of citrus polymethoxyflavones (PMFs), green tea extract, and lychee extract. We investigated the effect of dietary SlimTrym® on diet‐induced obesity ...and associated non‐alcoholic fatty liver disease (NAFLD) in mice.
Methods and results
Male C57BL/6 mice were fed a normal diet (ND), high fat diet (HFD) or HFD containing 0.1% or 0.5% SlimTrym® for 16 weeks. Dietary SlimTrym® significantly reduced weight gain and relative perigonadal, retroperitoneal, mesenteric fat weight as well as the size of adipocyte in HFD‐fed mice. SlimTrym® supplementation also effectively diminished hepatic steatosis and the serum levels of glutamate oxaloacetate transaminase (GOT), glutamate pyruvate transaminase (GPT), triacylglycerol (TG), and total cholesterol (TCHO). Down‐regulation of peroxisome proliferator‐activated receptor (PPAR)γ, sterol regulatory element‐binding protein (SREBP)‐1, and the activation of AMP‐activated protein kinase (AMPK) signaling by SlimTrym® in both adipose tissue and liver may be responsible for the observed anti‐obesity effects.
Conclusion
SlimTrym® supplementation potentially diminished diet‐induced obesity and hepatic steatosis via regulating AMPK signaling and molecules involved in lipid metabolism.
Dietary SlimTrym reduces hepatic lipogenic protein levels of C/EBP‐β, PPAR‐γ, SREBP‐1c, and FAS via increasing the activation of AMPK and down‐regulated ACC, resulting in reduce TG accumulation in adipocytes.
Intracellular galectins are carbohydrate-binding proteins capable of sensing and repairing damaged lysosomes. As in the physiological conditions glycosylated moieties are mostly in the lysosomal ...lumen but not cytosol, it is unclear whether galectins reside in lysosomes, bind to glycosylated proteins, and regulate lysosome functions. Here, we show in gut epithelial cells, galectin-9 is enriched in lysosomes and predominantly binds to lysosome-associated membrane protein 2 (Lamp2) in a Asn(N)-glycan dependent manner. At the steady state, galectin-9 binding to glycosylated Asn
of Lamp2 is essential for functionality of lysosomes and autophagy. Loss of N-glycan-binding capability of galectin-9 causes its complete depletion from lysosomes and defective autophagy, leading to increased endoplasmic reticulum (ER) stress preferentially in autophagy-active Paneth cells and acinar cells. Unresolved ER stress consequently causes cell degeneration or apoptosis that associates with colitis and pancreatic disorders in mice. Therefore, lysosomal galectins maintain homeostatic function of lysosomes to prevent organ pathogenesis.
There is little evidence on whether gender difference influences the incidence of subclinical coronary atherosclerosis in Asian populations with a 0 score.
In this study, we investigated the ...influence of age and gender on the extent of subclinical coronary atherosclerotic burden within a healthy Asian population with a 0 coronary artery calcium (CAC) score. A total of 934 participants (320 women and 614 men) from Taiwan's Han Chinese population with an initial CAC score of 0 were included in this study. They underwent 2 consecutive cardiac computed tomography scans over a clinical follow-up period of 4.35 ± 2.37 years. Clinical information and laboratory measurements were collected for analysis. Compared with the female group, the male group demonstrated significantly higher rates of subclinical CAC progression (27.4% vs 13.8%, p <0.001). Across the age group deciles (≤40, 41 to 50, 51 to 60, ≥61 years), the male group had a higher prevalence of subclinical CAC progression than the female group. For the subclinical CAC progression, the logistic regression model demonstrated that age, gender (male gender), cholesterol level, and follow-up period were statistically significant parameters. In conclusion, these findings support that a gender difference impacts the long-term natural course of subclinical coronary calcification conversion in women compared with men, suggesting that the gender-based effect on coronary CAC conversion plays an important role in subclinical coronary atherosclerosis risk stratification in personalized preventive medicine.
Polycyclic aromatic hydrocarbons (PAHs) are widespread environmental carcinogenic pollutants and they have become an important issue in food contamination. Dietary intake of PAHs has been recognized ...as a major route of human exposure. However, the mechanisms behind dietary PAH‐induced colorectal cancer (CRC) remain unclear. Several studies have shown that polymethoxyflavones (PMFs) are effective in preventing carcinogen‐induced CRC or colitis. In this study, we investigated the preventive effect of PMFs on benzoapyrene/dextran sulfate sodium (BaP/DSS)‐induced colorectal tumorigenesis in ICR mice. We found that PMFs significantly prevented BaP/DSS‐induced colorectal tumor formation. BaP mutagenic metabolite and DNA adducts were found to be reduced in colonic tissue in the PMFs‐treated groups through the modulation of BaP metabolism. At the molecular level, the results of RNA‐sequencing indicated that PMFs ameliorated BaP/DSS‐induced abnormal molecular mechanism change including activated inflammation, downregulated anti‐oxidation targets, and induced metastasis genes. The autophagic defect caused by BaP/DSS‐induced tumorigenesis was improved by pretreatment with PMFs. We found BaP/DSS‐induced CRC may be a Wnt/β‐catenin independent process. Additionally, consumption of PMFs extracts also altered the composition of gut microbiota and made it similar to that in the control group by increasing butyrate‐producing probiotics and decreasing CRC‐related bacteria. BaP in combination with DSS significantly induced colorectal tumorigenesis through induced DNA adduct formation, abnormal gene expression, and imbalanced gut microbiota composition. PMFs were a powerful preventive agent that suppressed BaP/DSS‐induced CRC via modulating multiple pathways as well as ameliorating autophagic defect. These results demonstrated for the first time the chemopreventive efficacy and comprehensive mechanisms of dietary PMFs for preventing BaP/DSS‐induced colorectal carcinogenesis.
What's new?
Carcinogenic polyaromatic hydrocarbons (PAHs) are pervasive in the environment and are a potential source of food contamination, with their ingestion via dietary sources greatly increasing colorectal cancer (CRC) risk. This study examined the possibility of preventing CRC induced by intake of the PAH benzoapyrene (BaP) via administration of polymethoxyflavones (PMFs), anticancer substances found in citrus peels. The results show that colon tumorigenesis induced by BaP and dextran sulfate sodium (DSS) in mice can be blocked by PMFs oral administration. PMFs were associated with reduced mutagenic metabolite levels and DNA adduct formation and with alleviation of a BaP/DSS‐induced autophagic defect.
Scope: Autophagy (type II programmed cell death) is crucial for maintaining cellular homeostasis. Several autophagy‐deficient or knockout studies indicate that autophagy is a tumor suppressor. ...Tetrahydrocurcumin (THC), a major metabolite of curcumin, has been demonstrated with anti‐colon carcinogenesis and antioxidation in vivo.
Methods and results: In the present study, we found that treatment with THC induced autophagic cell death in human HL‐60 promyelocytic leukemia cells by increasing autophage marker acidic vascular organelle (AVO) formation. Flow cytometry also confirmed that THC treatment did not increase sub‐G1 cell population whereas curcumin did with strong apoptosis‐inducing activity. At the molecular levels, the results from Western blot analysis showed that THC significantly down‐regulated phosphatidylinositol 3‐kinase/protein kinase B and mitogen‐activated protein kinase signalings including decreasing the phosphorylation of mammalian target of rapamycin, glycogen synthase kinase 3β and p70 ribosomal protein S6 kinase. Further molecular analysis exhibited that the pretreatment of 3‐methyladenine (an autophagy inhibitor) also significantly reduced acidic vascular organelle production in THC‐treated cells.
Conclusion: Taken together, these results demonstrated the anticancer efficacy of THC by inducing autophagy as well as provided a potential application for the prevention of human leukemia.
Approximately 5-7% of non-small cell lung cancer (NSCLC) cases harbor an anaplastic lymphoma kinase (ALK) fusion gene and may benefit from ALK inhibitor therapy. To detect ALK fusion genes, we ...developed a novel test using reverse transcription polymerase chain reaction (RT-PCR) for the ALK kinase domain (KD). Since ALK expression is mostly silenced in the adult with the exception of neuronal tissue, the normal lung tissue, mesothelial lining, and inflammatory cells are devoid of ALK transcript, making ALK KD RT-PCR an ideal surrogate test for ALK fusion transcripts in lung or pleural effusion. The test was designed with a short PCR product (197 bp) to work for both malignant pleural effusion (MPE) and formalin-fixed, paraffin-embedded (FFPE) NSCLC samples. Using ALK IHC as a reference, the sensitivity of the test was 100% for both MPE and FFPE. The specificity was 97.6% for MPE and 97.4% for FFPE. Two false positive cases were found. One was a metastatic brain lesion which should be avoided in the future due to intrinsic ALK expression in the neuronal tissue. The other one resulted from ALK gene amplification. Due to potential false positivity, subsequent confirmation tests such as fluorescence in situ hybridization or multiplex PCR would be preferable. Nevertheless, the test is simple and inexpensive with no false negativity, making it a desirable screening test. It also offers an advantage over multiplex RT-PCR with the capability to detect novel ALK fusions. Indeed through the screening test, we found a novel ALK fusion partner (sperm antigen with calponin homology and coiled-coil domains 1 like gene, SPECC1L) with increased sensitivity to crizotinib in vitro. In summary, a novel RNA-based ALK KD analysis was developed for ALK rearrangement screening in MPE and FFPE specimens of NSCLC. This simple inexpensive test can be implemented as routine diagnostics.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Playing online games is experience-oriented but few studies have explored the user’s initial (trial) reaction to game playing and how this further influences a player’s behavior. Drawing upon the ...Uses and Gratifications theory, we investigated players’ multiple gratifications for playing (i.e. achievement, enjoyment and social interaction) and their experience with the service mechanisms offered after they had played an online game. This study explores the important antecedents of players’ proactive “stickiness” to a specific online game and examines the relationships among these antecedents. The results show that both the gratifications and service mechanisms significantly affect a player’s continued motivation to play, which is crucial to a player’s proactive stickiness to an online game.
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