Chih-Jung Chang

Ganoderma lucidum reduces obesity in mice by modulating the composition of the gut microbiota

Obesity is associated with low-grade chronic inflammation and intestinal dysbiosis. Ganoderma lucidum is a medicinal mushroom used in traditional Chinese medicine with putative anti-diabetic effects. Here, we show that a water extract of Ganoderma lucidum mycelium (WEGL) reduces body weight, inflammation and insulin resistance in mice fed a high-fat diet (HFD). Our data indicate that WEGL not only reverses HFD-induced gut dysbiosis—as indicated by the decreased Firmicutes-to-Bacteroidetes ratios and endotoxin-bearing Proteobacteria levels—but also maintains intestinal barrier integrity and reduces metabolic endotoxemia. The anti-obesity and microbiota-modulating effects are transmissible via horizontal faeces transfer from WEGL-treated mice to HFD-fed mice. We further show that high molecular weight polysaccharides (>300 kDa) isolated from the WEGL extract produce similar anti-obesity and microbiota-modulating effects. Our results indicate that G. lucidum and its high molecular weight polysaccharides may be used as prebiotic agents to prevent gut dysbiosis and obesity-related metabolic disorders in obese individuals.

Identification of CD24 as a Cancer Stem Cell Marker in Human Nasopharyngeal Carcinoma

Cancer stem cells (CSCs) represent a unique sub-population of tumor cells with the ability to initiate tumor growth and sustain self-renewal. Although CSC biomarkers have been described for various tumors, only a few markers have been identified for nasopharyngeal carcinoma (NPC). In this study, we show that CD24+ cells isolated from human NPC cell lines express stem cell genes (Sox2, Oct4, Nanog, Bmi-1, and Rex-1), and show activation of the Wnt/β-catenin signaling pathway. CD24+ cells possess typical CSC characteristics that include enhanced cell proliferation, increased colony and sphere formation, maintenance of cell differentiation potential in prolonged culture, and enhanced resistance to chemotherapeutic drugs. Notably, CD24+ cells produce tumors following inoculation of as few as 500 cells in immunodeficient NOD/SCID mice. CD24+ cells further show increased invasion ability in vitro, which correlates with enhanced expression of matrix metalloproteinase 2 and 9. In summary, our results suggest that CD24 represents a novel CSC biomarker in NPC.

Anti-obesogenic and antidiabetic effects of plants and mushrooms

Obesity is reaching global epidemic proportions as a result of factors such as high-calorie diets and lack of physical exercise. Obesity is now considered to be a medical condition, which not only contributes to the risk of developing type 2 diabetes mellitus, cardiovascular disease and cancer, but also negatively affects longevity and quality of life. To combat this epidemic, anti-obesogenic approaches are required that are safe, widely available and inexpensive. Several plants and mushrooms that are consumed in traditional Chinese medicine or as nutraceuticals contain antioxidants, fibre and other phytochemicals, and have anti-obesogenic and antidiabetic effects through the modulation of diverse cellular and physiological pathways. These effects include appetite reduction, modulation of lipid absorption and metabolism, enhancement of insulin sensitivity, thermogenesis and changes in the gut microbiota. In this Review, we describe the molecular mechanisms that underlie the anti-obesogenic and antidiabetic effects of these plants and mushrooms, and propose that combining these food items with existing anti-obesogenic approaches might help to reduce obesity and its complications.

NK cells kill mycobacteria directly by releasing perforin and granulysin

Although the mechanisms underlying the cytotoxic effect of NK cells on tumor cells and intracellular bacteria have been studied extensively, it remains unclear how these cells kill extracellular bacterial pathogens. In this study, we examine how human NK cells kill Mycobacterium kansasii and M.tb. The underlying mechanism is contact dependent and requires two cytolytic proteins: perforin and granulysin. Mycobacteria induce enhanced expression of the cytolytic proteins via activation of the NKG2D/NCR cell‐surface receptors and intracellular signaling pathways involving ERK, JNK, and p38 MAPKs. These results suggest that NK cells use similar cellular mechanisms to kill both bacterial pathogens and target host cells. This report reveals a novel role for NK cells, perforin, and granulysin in killing mycobacteria and highlights a potential alternative defense mechanism that the immune system can use against mycobacterial infection.

cis-Resveratrol produces anti-inflammatory effects by inhibiting canonical and non-canonical inflammasomes in macrophages

Resveratrol, a natural phenolic compound found in red grapes and wine, exists as cis and trans isomers. Recent studies have shown that trans-resveratrol possesses anti-inflammatory, anti-oxidant, anti-carcinogenic, anti-tumor and immunomodulatory properties. However, it remains unclear whether cis-resveratrol may exhibit similar activities. The objective of the present study was to examine the effects of cis- and trans-resveratrol on the production of pro-inflammatory cytokines and mediators in human macrophages. We examined the possibility that cis- and trans-resveratrol may affect cytokine secretion by modulating inflammasomes, intracellular multi-protein complexes, the assembly of which leads to caspase-1 activation and secretion of active IL-1β by macrophages. Our results show that pre-treatment of macrophages with cis-resveratrol not only reduces pro-IL-1β production and IL-1β secretion, but also suppresses ATP-induced transcription and activation of caspase-1 and caspase-4. Notably, cis-resveratrol inhibits the expression of the purinergic receptor, P2X7R, and the endoplasmic reticulum stress marker, Glc-regulated protein 78, but also reduces reactive oxygen species production. Moreover, cis-resveratrol attenuates cyclooxygenase-2 expression and prostaglandin E2 production. cis-Resveratrol also decreases the phosphorylation of p38 MAPK and expression of the c-Jun protein. These results indicate that cis-resveratrol produces anti-inflammatory effects by inhibiting both the canonical and non-canonical inflammasomes, and associated pathways in human macrophages.

Effects of post materials and length on the stress distribution of endodontically treated maxillary central incisors: a 3D finite element analysis.

Traditionally, using a long post can cause progressive removal of the root structure, complicate the ability to re-treat the tooth if necessary and make it difficult to apply an adhesive bonding agent into the root canal. It is unclear if a shorter post length can be applied when a light translucent glass fibre post and adhesive resin cement are used. The aim of this study was to evaluate the biomechanical performance of endodontically treated teeth restored with three post materials, glass-fibre, stainless steel and cast-nickel chromium posts and cores of different lengths of 7, 10 and 13 mm. A 3D finite element analysis model of the maxillary central incisor was constructed. An occlusal load of 300 N was applied to a node at the palatal surface of the crown at 45 degrees to the long axis of the tooth. von Mises stress analyses were carried out in three regions. Simulated data were collected for plotting various pattern graphics and conducting statistical tests. The pattern graphics showed that when the post length changed from 13 to 7 mm, the stress patterns were even and flat in all fibre-post groups, while the stress patterns of the metal-post groups showed an M-shaped peak and trough. Statistical tests showed that the shorter fibre post was superior to the longer metal post in some situations. Within the limitations of this study, it was concluded that when a metal post is used, the post should be as long as possible, while the biomechanical performance of a glass-fibre post combined with a composite resin core was less sensitive to post length.

Ganoderma lucidum stimulates NK cell cytotoxicity by inducing NKG2D/NCR activation and secretion of perforin and granulysin

Ganoderma lucidum (G. lucidum) is a medicinal mushroom long used in Asia as a folk remedy to promote health and longevity. Recent studies indicate that G. lucidum activates NK cells, but the molecular mechanism underlying this effect has not been studied so far. To address this question, we prepared a water extract of G. lucidum and examined its effect on NK cells. We observed that G. lucidum treatment increases NK cell cytotoxicity by stimulating secretion of perforin and granulysin. The mechanism of activation involves an increased expression of NKG2D and natural cytotoxicity receptors (NCRs), as well as increased phosphorylation of intracellular MAPKs. Our results indicate that G. lucidum induces NK cell cytotoxicity against various cancer cell lines by activating NKG2D/NCR receptors and MAPK signaling pathways, which together culminate in exocytosis of perforin and granulysin. These observations provide a cellular and molecular mechanism to account for the reported anticancer effects of G. lucidum extracts in humans.

Effects of obesity on depression: A role for inflammation and the gut microbiota

Depression is a mental disorder associated with environmental, genetic and psychological factors. Recent studies indicate that chronic neuro-inflammation may affect brain physiology and alter mood and behavior. Consumption of a high-fat diet leads to obesity and chronic systemic inflammation. The gut microbiota mediates many effects of a high-fat diet on human physiology and may also influence the mood and behavior of the host. We review here recent studies suggesting the existence of a link between obesity, the gut microbiota and depression, focusing on the mechanisms underlying the effects of a high-fat diet on chronic inflammation and brain physiology. This body of research suggests that modulating the composition of the gut microbiota using prebiotics and probiotics may produce beneficial effects on anxiety and depression.

Activation of NK cell cytotoxicity by the natural compound 2,3-butanediol

The natural compound 2,3‐BTD has diverse physiological effects in a range of organisms, including acting as a detoxifying product of liver alcohol metabolism in humans and ameliorating endotoxin‐induced acute lung injury in rats. In this study, we reveal that 2,3‐BTD enhances NK cell cytotoxic activity in human pNK cells and NK92 cells. Treatment of NK cells with 2,3‐BTD increased perforin expression in a dose‐dependent manner. This was accompanied by elevated JNK and ERK1/2 MAPK activities and enhanced expression of NKG2D/NCRs, upstream signaling molecules of the MAPK pathways. The 2,3‐BTD effect was inhibited by pretreatment with inhibitors of JNK (SP) or ERK1/2 (PD) or by depleting NKG2D/NCRs or JNK1 or ERK2 with siRNA. These results indicate that 2,3‐BTD activates NK cell cytotoxicity by NKG2D/NCR pathways and represent the first report of the 2,3‐BTD effect on activation of innate immunity cells.

Corrigendum: Ganoderma lucidum reduces obesity in mice by modulating the composition of the gut microbiota

This corrects the article DOI: 10.1038/ncomms8489.