Integrated Analysis of Gut Microbiome and Adipose Transcriptome Reveals Beneficial Effects of Resistant Dextrin from Wheat Starch on Insulin Resistance in Kunming Mice.

Systemic chronic inflammation is recognized as a significant contributor to the development of obesity-related insulin resistance. Previous studies have revealed the physiological benefits of resistant dextrin (RD), including obesity reduction, lower fasting glucose levels, and anti-inflammation. The present study investigated the effects of RD intervention on insulin resistance (IR) in Kunming mice, expounding the mechanisms through the gut microbiome and transcriptome of white adipose. In this eight-week study, we investigated changes in tissue weight, glucose-lipid metabolism levels, serum inflammation levels, and lesions of epididymal white adipose tissue (eWAT) evaluated via Hematoxylin and Eosin (H&E) staining. Moreover, we analyzed the gut microbiota composition and transcriptome of eWAT to assess the potential protective effects of RD intervention. Compared with a high-fat, high-sugar diet (HFHSD) group, the RD intervention significantly enhanced glucose homeostasis (e.g., AUC-OGTT, HOMA-IR, p < 0.001), and reduced lipid metabolism (e.g., TG, LDL-C, p < 0.001) and serum inflammation levels (e.g., IL-1ß, IL-6, p < 0.001). The RD intervention also led to changes in the gut microbiota composition, with an increase in the abundance of probiotics (e.g., Parabacteroides, Faecalibaculum, and Muribaculum, p < 0.05) and a decrease in harmful bacteria (Colidextribacter, p < 0.05). Moreover, the RD intervention had a noticeable effect on the gene transcription profile of eWAT, and KEGG enrichment analysis revealed that differential genes were enriched in PI3K/AKT, AMPK, in glucose-lipid metabolism, and in the regulation of lipolysis in adipocytes signaling pathways. The findings demonstrated that RD not only ameliorated IR, but also remodeled the gut microbiota and modified the transcriptome profile of eWAT.

Areca nut extracts exert different effects in oral cancer cells depending on serum concentration: A clue to the various oral alterations in betel quid chewers.

Betel quid chewing is associated with various pathologic alterations in oral mucosa. However, the molecular mechanism behind so many contradictory alterations remains unclear. Here we aimed to build a model to facilitate the related studies in cultured cells. In our results, areca nut extract (ANE) was found to exert different effects in oral cells depending on the supplemented serum level. ANE strongly induced DNA damage, necrotic ballooning, and inflammatory cytokines under lower serum concentration while might convert to facilitate deregulated growth of serum-supplemented cells via modulating the activity/expression of factors such as E-cadherin and Snail. Despite ANE significantly activated NF-κB, a mediator critical for inflammation, inhibition of NF-κB did not prevent the activation of IL8 promoter. We further discovered Y705-dephosphorylated STAT3 might enhance IL8 transcription. Since necrosis and the inflammatory cytokines could cause massive inflammation, infiltration of interstitial fluid might potentiate cellular resistance against the acute cytotoxicity of ANE and further support the proliferation of transforming cells. Induction of VEGF and angiogenesis under lower serum condition also paved the way for cell growth and subsequent metastasis. Accordingly, we concluded that in correlation with serum infiltration ANE caused particular effects in oral cells and possibly the various clinicopathological alterations in vivo.

Areca nut extract induces pyknotic necrosis in serum-starved oral cells via increasing reactive oxygen species and inhibiting GSK3ß: an implication for cytopathic effects in betel quid chewers.

Areca nut has been proven to be correlated with various pathologic alterations in oral cavity. However, the mechanisms for such cytopathic effects are still elusive due mostly to the limitations of cell culture systems. Here we discovered that areca nut extract (ANE) induced production of autophagosome vacuoles in cells cultured with rich medium but induced pyknosis and ballooning, two morphological alterations frequently observed in betel quid chewers, in cells under a serum-free culture condition. Permeability of the serum-starved cells to propidium iodide (PI) confirmed ANE induced novel necrosis with pyknosis (pyknotic necrosis), providing a possible explanation for inflammatory infiltration in chewers' mucosa. In these serum-starved cells, ANE strongly induced reactive oxygen species (ROS), which acted as a key switch for the initiation of pyknotic necrosis. Calcium flux was also involved in the morphological alterations. Besides, inhibition of GSK3ß by SB216763 significantly exacerbated the pyknotic necrosis either induced by ANE or H2O2 in serum-starved cells, suggesting that GSK3ß is a critical regulator for ANE/ROS-mediated pyknotic necrosis. Interestingly, LC3-II transition and PARP cleavage were still detected in the serum-starved cells after ANE treatment, suggesting concurrent activation of apoptotic and autophagic pathways. Finally, insulin could counteract the effect of ANE-induced pyknotic necrosis. Taken together, these data provide a platform for studying ANE-induced cytopathogenesis and the first clinical implication for several pathological alterations, such as ballooning and inflammatory infiltration, in betel quid chewers.

[Study of the correlation between polycyclic aromatic hydrocarbons exposure during pregnancy and neonatal neurobehavioral development in Taiyuan and Changzhi cities].

OBJECTIVE: To compare the difference of polycyclic aromatic hydrocarbons (PAHs) levels in the urban air and the scores of Neonatal Behavioral Neurological Assessment (NBNA) between Taiyuan and Changzhi cities and to explore the effects of PAHs in the urban air during pregnancy on neonatal behavioral neurological development. METHODS: High-performance liquid chromatography (HPLC) with subsequent fluorescence detection was used to determine the PAHs levels in the cooperational hospitals in Changzhi and Taiyuan cities and the urinary 1-hydroxypyrene levels of the 297 pregnant women living Changzhi and Taiyuan cities during Nov. 2009 to May 2010. NBNA was used to determine the development of neonatal neural behavior. The differences of PAHs levels in the urban air, the pregnant women urinary 1-hydroxypyrene levels and NBNA scores between Taiyuan and Changzhi were compared. RESULTS: There are significant differences of levels of pyrene, benz [a] anthracene, Chrysene, benz [a] pyrene, dibenz [a, h] anthracene in the urban air between Taiyuan and Changzhi (P < 0.10). The median of urinary 1-hydroxypyrene levels in pregnant women of Taiyuan was 1.140 microg/mmolCr, (P25 was 0.457 microg/mmolCr, P75 was 2.678 microg/mmolCr), the median of urinary 1-hydroxypyrene levels in pregnant women of Changzhi was 0.761 microg/mmolCr, (P25 was 0.133 microg/mmolCr, P75 was 2.095 microg/mmolCr). There are significant differences of urinary 1-hydroxypyrene levels in pregnant women between Taiyuan and Changzhi (t = -3.140, P = 0.002). There are significant differences of the NBNA scores, capacity scores, passive muscle tension scores, active muscle tension scores and general assessment scores between Taiyuan and Changzhi (P < 0.10). There was correlation between NBNA scores and urinary 1-hydroxypyrene level in pregnant women. CONCLUSION: The PAHs in the urban air during pregnancy may adversely affect the neonatal neurobehavioral development.

Arecoline downregulates levels of p21 and p27 through the reactive oxygen species/mTOR complex 1 pathway and may contribute to oral squamous cell carcinoma.

Arecoline, the major alkaloid of areca nut, has been shown to cause strong genotoxicity and is considered a potential carcinogen. However, the detailed mechanism for arecoline-induced carcinogenesis remains obscure. In this study, we noticed that the levels of p21 and p27 increased in two oral squamous cell carcinoma cell lines with high confluence. Furthermore, when treated with arecoline, elevated levels of p21 and p27 could be downregulated through the reactive oxygen species/mTOR complex 1 (ROS/mTORC1) pathway. Although arecoline decreased the activity of mTORC1, the amounts of autophagosome-like vacuoles or type II LC3 remained unchanged, suggesting that the downregulation of p21 and p27 was independent of autophagy-mediated protein destruction. Arecoline also caused DNA damage through ROS, indicating that the reduced levels of p21 and p27 might facilitate G (1) /S transition of the cell cycle and subsequently lead to error-prone DNA replication. In conclusion, these data have provided a possible mechanism for arecoline-induced carcinogenesis in subcytolytic doses in vivo.

[Research of GAP implement supporting system of Chinese medicine plant].

The paper presented a total system frame of supporting GAP implement of Chinese medicine plant in which information technology played an important role. A supporting system of GAP implement have been demonstrated on the GAP base in Zhangshu, Jiangxi.