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The process of heat regulation is complex and its exact molecular mechanism is not fully understood. In this study, to investigate the global gene regulation response to acute heat exposure, gene microarrays were exploited to analyze the effects of heat stress on three tissues (brain, liver, leg muscle) of the yellow broiler chicken (Gallus gallus). We detected 166 differentially expressed genes (DEGs) in the brain, 219 in the leg muscle and 317 in the liver. Six of these genes were differentially expressed in all three tissues and were validated by qRT-PCR, and included heat shock protein genes (HSPH1, HSP25), apoptosis-related genes (RB1CC1, BAG3), a cell proliferation and differentiation-related gene (ID1) and the hunger and energy metabolism related gene (PDK). All these genes might be important factors in chickens suffering from heat stress. We constructed gene co-expression networks using the DEGs of the brain, leg muscle and liver and two, four and two gene co-expression modules were identified in these tissues, respectively. Functional enrichment of these gene modules revealed that various functional clusters were related to the effects of heat stress, including those for cytoskeleton, extracellular space, ion binding and energy metabolism. We concluded that these genes and functional clusters might be important factors in chickens under acute heat stress. Further in-depth research on the newly discovered heat-related genes and functional clusters is required to fully understand their molecular functions in thermoregulation., (Copyright © 2014 Elsevier B.V. All rights reserved.)

Jian Zuo,1– 3,* Meng-Qing Tao,1,3,* Xin-Yue Wu,4 Tian-Tian Jiang,1 Opeyemi Joshua Olatunji,5 Jiyang Dong,4 Jun Han,6 Cong-Lan Ji7 1Department of Traditional Chinese Medicine, The First Affiliated Hospital of Wannan Medical College (Yijishan Hospital), Wuhu, 241000, People’s Republic of China; 2Key Laboratory of Non-coding RNA Transformation Research of Anhui Higher Education Institution, Wannan Medical College, Wuhu, 241000, People’s Republic of China; 3Research Center of Integration of Traditional Chinese and Western Medicine, Wannan Medical College, Wuhu, 241000, People’s Republic of China; 4Department of Electronic Science, Xiamen University, Xiamen, 361005, People’s Republic of China; 5Faculty of Traditional Thai Medicine, Prince of Songkla University, Hat Yai, 90112, Thailand; 6Drug Research and Development Center, School of Pharmacy, Wannan Medical College, Wuhu, 241000, Anhui, People’s Republic of China; 7School of Pharmacy, Anhui College of Traditional Chinese Medicine, Wuhu, 241000, Anhui, People’s Republic of China*These authors contributed equally to this workCorrespondence: Jun HanDrug Research and Development Center, School of Pharmacy, Wannan Medical College, Wuhu, 241000, Anhui, People’s Republic of ChinaEmail hanjun@wnmc.edu.cnCong-Lan JiSchool of Pharmacy, Anhui College of Traditional Chinese Medicine, Wuhu, 241000, Anhui, People’s Republic of ChinaEmail 37709103@qq.comBackground: The bark of Securidaca inappendiculata Hassk. is traditionally used for treating inflammatory diseases and bone fractures in China. We have previously validated the xanthone-enriched fraction (XRF) of S. inappendiculata with anti-rheumatic potentials, but mechanism underlying the joints protective effects is still largely unknown.Materials and Methods: The male rats with collagen-induced arthritis (CIA) were treated with XRF. The therapeutic efficacy of XRF was evaluated by arthritis score changes, morphological observation of paws, histological examinations and serological analyses. Protein expression in tissues and cells was investigated by either immunohistochemical or immunoblotting methods, while levels of mRNA expression were investigated by RT-qPCR. Metabolites in serum were detected by LC-MS approach. The joints homogenates were used for analyzing possible targeted genes by genome microarray analyses.Results: Treatment with XRF and methotrexate (MTX) led to significant decrease in arthritis scores, and alleviated deformation of paws in CIA rats. In addition, XRF and MTX reduced circulating TNF-α, IL-1β and IL-17α in the serum and down-regulated TLR4/NF-κB and JNK pathways in joints of CIA rats. Compared to MTX, XRF-loading microemulsion significantly protected joints, which was accompanied by dramatic decrease in MMP3. Differential genes-based KEGG enrichment and metabolomics analysis suggested that XRF reduced fatty acids biosynthesis by regulating PPAR-γ signaling. S inappendiculata-derived 1,7-dihydroxy-3,4-dimethoxyxanthone (XAN) up-regulated PPAR-γ expression in macrophages, but suppressed it in pre-adipocytes in vitro, which was synchronized with SIRT1 changes. Adiponectin production and SCD-1 expression in pre-adipocytes were also decreased. Aside the direct inhibition on MMP3 expression in synovioblast, the presence of XAN in macrophages-pre-adipocytes co-culture system further reinforced this effect.Conclusion: This study revealed the joint protective advantages of the bioactive fraction from S. inappendiculata in CIA rats over MTX, and demonstrated that S. inappendiculata-derived xanthones suppressed the erosive nature of synovioblast acquired under inflammatory circumstances by regulating PPAR-γ signaling-controlled metabolism-immunity feedback.Keywords: peroxisome proliferators-activated receptor gamma, PPAR-γ, energy metabolism, rheumatoid arthritis, metabolomics, macrophage, inflammation