Gang Liu

Bio: Gang Liu is an academic researcher from Hunan Agricultural University. The author has contributed to research in topics: Gut flora & Circadian rhythm. The author has an hindex of 4, co-authored 15 publications receiving 64 citations.

Mitochondria-Targeted Antioxidants: A Step towards Disease Treatment

Abstract: Mitochondria are the main organelles that produce adenosine 5'-triphosphate (ATP) and reactive oxygen species (ROS) in eukaryotic cells and meanwhile susceptible to oxidative damage. The irreversible oxidative damage in mitochondria has been implicated in various human diseases. Increasing evidence indicates the therapeutic potential of mitochondria-targeted antioxidants (MTAs) for oxidative damage-associated diseases. In this article, we introduce the advantageous properties of MTAs compared with the conventional (nontargeted) ones, review different mitochondria-targeted delivery systems and antioxidants, and summarize their experimental results for various disease treatments in different animal models and clinical trials. The combined evidence demonstrates that mitochondrial redox homeostasis is a potential target for disease treatment. Meanwhile, the limitations and prospects for exploiting MTAs are discussed, which might pave ways for further trial design and drug development.

Administration of Exogenous Melatonin Improves the Diurnal Rhythms of the Gut Microbiota in Mice Fed a High-Fat Diet.

Abstract: Melatonin, a circadian hormone, has been reported to improve host lipid metabolism by reprogramming the gut microbiota, which also exhibits rhythmicity in a light/dark cycle. However, the effect of the administration of exogenous melatonin on the diurnal variation in the gut microbiota in mice fed a high-fat diet (HFD) is unclear. Here, we further confirmed the antiobesogenic effect of melatonin on mice fed an HFD for 2 weeks. Samples were collected every 4 h within a 24-h period, and diurnal rhythms of clock gene expression (Clock, Cry1, Cry2, Per1, and Per2) and serum lipid indexes varied with diurnal time. Notably, Clock and triglycerides (TG) showed a marked rhythm in the control in melatonin-treated mice but not in the HFD-fed mice. The rhythmicity of these parameters was similar between the control and melatonin-treated HFD-fed mice compared with that in the HFD group, indicating an improvement caused by melatonin in the diurnal clock of host metabolism in HFD-fed mice. Moreover, 16S rRNA gene sequencing showed that most microbes exhibited daily rhythmicity, and the trends were different for different groups and at different time points. We also identified several specific microbes that correlated with the circadian clock genes and serum lipid indexes, which might indicate the potential mechanism of action of melatonin in HFD-fed mice. In addition, effects of melatonin exposure during daytime or nighttime were compared, but a nonsignificant difference was noticed in response to HFD-induced lipid dysmetabolism. Interestingly, the responses of microbiota-transplanted mice to HFD feeding also varied at different transplantation times (8:00 and 16:00) and with different microbiota donors. In summary, the daily oscillations in the expression of circadian clock genes, serum lipid indexes, and the gut microbiota appeared to be driven by short-term feeding of an HFD, while administration of exogenous melatonin improved the composition and diurnal rhythmicity of some specific gut microbiota in HFD-fed mice.IMPORTANCE The gut microbiota is strongly shaped by a high-fat diet, and obese humans and animals are characterized by low gut microbial diversity and impaired gut microbiota compositions. Comprehensive data on mammalian gut metagenomes shows gut microbiota exhibit circadian rhythms, which is disturbed by a high-fat diet. On the other hand, melatonin is a natural and ubiquitous molecule showing multiple mechanisms of regulating the circadian clock and lipid metabolism, while the role of melatonin in the regulation of the diurnal patterns of gut microbial structure and function in obese animals is not yet known. This study delineates an intricate picture of melatonin-gut microbiota circadian rhythms and may provide insight for obesity intervention.

Roles of Macrophages in the Development and Treatment of Gut Inflammation.

Abstract: Macrophages, which are functional plasticity cells, have the ability to phagocytize and digest foreign substances and acquire pro-(M1-like) or anti-inflammatory (M2-like) phenotypes according to their microenvironment. The large number of macrophages in the intestinal tract, play a significant role in maintaining the homeostasis of microorganisms on the surface of the intestinal mucosa and in the continuous renewal of intestinal epithelial cells. They are not only responsible for innate immunity, but also participate in the development of intestinal inflammation. A clear understanding of the function of macrophages, as well as their role in pathogens and inflammatory response, will delineate the next steps in the treatment of intestinal inflammatory diseases. In this review, we discuss the origin and development of macrophages and their role in the intestinal inflammatory response or infection. In addition, the effects of macrophages in the occurrence and development of inflammatory bowel disease (IBD), and their role in inducing fibrosis, activating T cells, reducing colitis, and treating intestinal inflammation were also reviewed in this paper.

Epigallocatechin Gallate Can Protect Mice From Acute Stress Induced by LPS While Stabilizing Gut Microbes and Serum Metabolites Levels.

Abstract: Epigallocatechin gallate (EGCG) has potent biological activity as well as strong antioxidant and anti-inflammatory effects. This study aims to explore the protective effect of EGCG on LPS-induced acute injury. We randomly divided 18 mice into three groups: CON, LPS, and EGCG-LPS. We gave the EGCG-LPS group gavage treatment with EGCG on day 8-15 and an intraperitoneal injection of LPS on day 16 to induce acute injury. The results showed that, compared with the LPS group, the bodyweight of the mice in the EGCG-LPS group increased significantly and effectively inhibited the morphological damage of the jejunum and liver. We measured liver tissue and found that the EGCG gavage treatment significantly inhibited the pro-inflammatory factors (TNF-α, IL-1β, IL-6, MCP-1, MIP-2, IFN-γ) and oxidation indicators (MPO, NO, ALT, and AST) levels increase. The microbiological results showed that the EGCG gavage treatment reshaped the disturbance done to the intestinal microbial community in the mice by LPS, reversed the changes in the abundance ratio of Firmicutes/Bacteroidetes, and significantly reduced the abundance of Enterobacteriales. Finally, the serum metabolomics results showed that, when compared with the LPS group, the gavage treatment of EGCG significantly increased the concentration of sphingomyelin (d17:1/17:0), sphingomyelin (d16:1/20:0), and significantly reduced the content of trans-Hexadec-2-enoyl carnitine, and so on. Therefore, we believe that EGCG can protect mice from acute stress induced by LPS while stabilizing gut microbes in general, improving the metabolism of sphingolipids, and inhibiting the content of harmful metabolites.

Potential role of Lactobacillus plantarum in colitis induced by dextran sulfate sodium through altering gut microbiota and host metabolism in murine model

Abstract: Inflammatory bowel disease (IBD) is a chronic lifelong disease characterized by inflammation of the gastrointestinal tract. Although more and more treatment options serve IBD, there is still no cure. It is important to find an effective treatment for IBD. This study aims to investigate whether Lactobacillus plantarum (L. plantarum) could alleviate colitis induced by dextran sulfate sodium (DSS). Following the DSS challenge, L. plantarum on DSS-mediated inflammatory colon lesions in mice, and L. plantarum therapy heightened the relative abundance of the colon-resident Actinobacteria. Analysis of serum metabolomics also indicated that the content of MG (18:4 (6Z, 9Z, 12Z, 15Z)/0:0/0:0) was increased in response to L. plantarum therapy, and this was also the case for indolepyruvate and 1-hydroxyibuprofen. However, 13-oxooctadecadienoic acid (13-oxoODE) and indolylacryloylglycine content fell following the DSS challenge. Based on these results, the study elucidates the mitigatory effects of L. plantarum in colitis, which depend on its regulation of the colonic microbial community and its modification of serum metabolites. The results revealed that L. plantarum mitigated inflammatory colon lesions, reprogrammed the microbial community and altered the level of serum metabolites in a murine model challenged with DSS. The study may present a potential therapeutic strategy for colitis.

Neuroinflammation in Alzheimer's Disease.

Abstract: Alzheimer’s disease (AD) is a neurodegenerative disease associated with human aging. Ten percent of individuals over 65 years have AD and its prevalence continues to rise with increasing age. There are currently no effective disease modifying treatments for AD, resulting in increasingly large socioeconomic and personal costs. Increasing age is associated with an increase in low-grade chronic inflammation (inflammaging) that may contribute to the neurodegenerative process in AD. Although the exact mechanisms remain unclear, aberrant elevation of reactive oxygen and nitrogen species (RONS) levels from several endogenous and exogenous processes in the brain may not only affect cell signaling, but also trigger cellular senescence, inflammation, and pyroptosis. Moreover, a compromised immune privilege of the brain that allows the infiltration of peripheral immune cells and infectious agents may play a role. Additionally, meta-inflammation as well as gut microbiota dysbiosis may drive the neuroinflammatory process. Considering that inflammatory/immune pathways are dysregulated in parallel with cognitive dysfunction in AD, elucidating the relationship between the central nervous system and the immune system may facilitate the development of a safe and effective therapy for AD. We discuss some current ideas on processes in inflammaging that appear to drive the neurodegenerative process in AD and summarize details on a few immunomodulatory strategies being developed to selectively target the detrimental aspects of neuroinflammation without affecting defense mechanisms against pathogens and tissue damage.

Circadian rhythms and obesity: Timekeeping governs lipid metabolism.

Abstract: Almost all living organisms have evolved autoregulatory transcriptional-translational feedback loops that produce oscillations with a period of approximately 24-h. These endogenous time keeping mechanisms are called circadian clocks. The main function of these circadian clocks is to drive overt circadian rhythms in the physiology of the organisms to ensure that main physiological functions are in synchrony with the external environment. Disruption of circadian rhythms caused by genetic or environmental factors has long-term consequences for metabolic health. Of relevance, host circadian rhythmicity and lipid metabolism are increasingly recognized to cross-regulate and the circadian clock-lipid metabolism interplay may involve in the development of obesity. Multiple systemic and molecular mechanisms, such as hormones (ie, melatonin, leptin, and glucocorticoid), the gut microbiome, and energy metabolism, link the circadian clock and lipid metabolism, and predictably, the deregulation of circadian clock-lipid metabolism interplay can increase the risk of obesity, which in turn may exacerbate circadian disorganization. Feeding time and dietary nutrients are two of key environmental Zeitgebers affecting the circadian rhythm-lipid metabolism interplay, and the influencing mechanisms in obesity development are highlighted in this review. Together, the characterization of the clock machinery in lipid metabolism aimed at producing a healthy circadian lifestyle may improve obesity care.

Melatonin in humans

Abstract: Melatonin, the hormone of the pineal gland, received a great deal of attention in the last decade because of its availability as over-the-counter drug or food supplement in some countries and suggested role in many vital physiological processes. Melatonin secretion is not restricted to mammals but is also produced in nonmammalian vertebrates, in some invertebrates, and in many plants, with the same molecular structure. The synthesis of melatonin is strictly controlled by lighting conditions and shows a clear circadian rhythm with low values during the daytime and significant increase at night. In this survey the basic data on melatonin significance in human physiology and in pathological processes as well as its possible therapeutic significance are reviewed and discussed.

Gut Microbiota and Diarrhea: An Updated Review.

Abstract: Diarrhea is a common problem to the whole world and the occurrence of diarrhea is highly associated with gut microbiota, such as bacteria, fungi, and viruses. Generally, diarrheal patients or animals are characterized by gut microbiota dysbiosis and pathogen infections may lead to diarrheal phenotypes. Of relevance, reprograming gut microbiota communities by dietary probiotics or fecal bacteria transplantation are widely introduced to treat or prevent diarrhea. In this review, we discussed the influence of the gut microbiota in the infection of diarrhea pathogens, and updated the research of reshaping the gut microbiota to prevent or treat diarrhea for the past few years. Together, gut microbiota manipulation is of great significance to the prevention and treatment of diarrhea, and further insight into the function of the gut microbiota will help to discover more anti-diarrhea probiotics.

Inflammasomes in Alveolar Bone Loss

Abstract: Bone remodeling is tightly controlled by osteoclast-mediated bone resorption and osteoblast-mediated bone formation. Fine tuning of the osteoclast-osteoblast balance results in strict synchronization of bone resorption and formation, which maintains structural integrity and bone tissue homeostasis; in contrast, dysregulated bone remodeling may cause pathological osteolysis, in which inflammation plays a vital role in promoting bone destruction. The alveolar bone presents high turnover rate, complex associations with the tooth and periodontium, and susceptibility to oral pathogenic insults and mechanical stress, which enhance its complexity in host defense and bone remodeling. Alveolar bone loss is also involved in systemic bone destruction and is affected by medication or systemic pathological factors. Therefore, it is essential to investigate the osteoimmunological mechanisms involved in the dysregulation of alveolar bone remodeling. The inflammasome is a supramolecular protein complex assembled in response to pattern recognition receptors and damage-associated molecular patterns, leading to the maturation and secretion of pro-inflammatory cytokines and activation of inflammatory responses. Pyroptosis downstream of inflammasome activation also facilitates the clearance of intracellular pathogens and irritants. However, inadequate or excessive activity of the inflammasome may allow for persistent infection and infection spreading or uncontrolled destruction of the alveolar bone, as commonly observed in periodontitis, periapical periodontitis, peri-implantitis, orthodontic tooth movement, medication-related osteonecrosis of the jaw, nonsterile or sterile osteomyelitis of the jaw, and osteoporosis. In this review, we present a framework for understanding the role and mechanism of canonical and noncanonical inflammasomes in the pathogenesis and development of etiologically diverse diseases associated with alveolar bone loss. Inappropriate inflammasome activation may drive alveolar osteolysis by regulating cellular players, including osteoclasts, osteoblasts, osteocytes, periodontal ligament cells, macrophages, monocytes, neutrophils, and adaptive immune cells, such as T helper 17 cells, causing increased osteoclast activity, decreased osteoblast activity, and enhanced periodontium inflammation by creating a pro-inflammatory milieu in a context- and cell type-dependent manner. We also discuss promising therapeutic strategies targeting inappropriate inflammasome activity in the treatment of alveolar bone loss. Novel strategies for inhibiting inflammasome signaling may facilitate the development of versatile drugs that carefully balance the beneficial contributions of inflammasomes to host defense.