A New Class of Molecules from Staphylococcus Species Affects Quorum Sensing and Growth of Gram-Negative Bacteria

This thesis addressed bacterial communication between Gram positive and Gram negative bacteria. The knowledge that many pathogens rely on cell-to-cell communication mechanisms known as quorum sensing, opens a new disease control strategy: quorum quenching. While studying the interaction of staphylococci with Gram-negative bacteria, we came across another communication system in a Staphylococcus intermedius group (SIG) species which can act as a zoonotic pathogen. This is one of the rare examples where Gram-positive bacteria excrete two compounds in comparatively high amounts that suppress the quorum sensing signaling and inhibit the growth of a broad spectrum of Gram-negative beta- and gamma-proteobacteria. The excreted compounds, named yayurea A and B, were isolated from S. delphini and structurally characterized. In vitro studies with the Nacyl homoserine lactone (AHL) responding receptor LuxN of V. harveyi indicated that both compounds stimulated the LuxN-mediated phosphorylation of LuxU and caused the opposite effects with AHL. Furthermore, growth of yayurea A and B producing S. delphini is not suppressed by respiratory toxins when co-cultured with P. aeruginosa. Taken together, yayureas are presumably involved in self-protection and ensuring competitiveness in natural environments shared with Gram-negatives. In the second part of thesis, the role of protein A in Staphylococcus aureus adhesion to ethylene glycol coated surfaces was investigated. It was found that the coating materials, HS(CH2)11EG3OMe (EG3OMe) and poly-ethylene-glycol (PEG) prevented bacterial adhesion of S. aureus cells. However, pretreatment of EG3OMe and PEG coatings with r-globulins or serum strongly promoted adherence of S. aureus cell. Furthermore, the spa-deletion mutant S. aureus, lacking the IgG binding protein A, showed reduced adherence and pretreatment of S. aureus with serum significantly decreased adherence. These results suggested that r-globulins play a crucial role in promoting S. aureus cells adhesion by its IgG binding proteins. Particularly γglobulins bound to the coated surfaces thus mediating adherence of S. aureus via its protein A. Intercepting this adherence should prove to be useful in preventing biofilm formation

THE COMPARISON OF DIFFERENT ELASTIC TENSION OF KINESIO TAPING ON GASTROCNEMIUS MUSCLE ACTIVATION

The purpose of this study was to compare the effect of different elastic tension of Kinesio taping on gastrocnemius muscle activation. Thirty-seven healthy athletes was recruited and randomly divided into three groups: Elastic tension 0% (N = 13), 10% (N = 12), and 20% (N = 12). All athletes were applied Kinesio taping on gastrocnemius muscle in 3 different elastic tape tensions. The wireless electromyography was used to assess the gastrocnemius muscle activation before and after applied Kinesio taping while jogging on treadmill. The results showed that a significant interaction between different elastic tape tension and pre-post taping applied (

Assessment of mitochondrial dysfunction and implications in cardiovascular disorders

Mitochondria play a pivotal role in cellular function, not only acting as the powerhouse of the cell, but also regulating ATP synthesis, reactive oxygen species (ROS) production, intracellular Ca2+ cycling, and apoptosis. During the past decade, extensive progress has been made in the technology to assess mitochondrial functions and accumulating evidences have shown that mitochondrial dysfunction is a key pathophysiological mechanism for many diseases including cardiovascular disorders, such as ischemic heart disease, cardiomyopathy, hypertension, atherosclerosis, and hemorrhagic shock. The advances in methodology have been accelerating our understanding of mitochondrial molecular structure and function, biogenesis and ROS and energy production, which facilitates new drug target identification and therapeutic strategy development for mitochondrial dysfunction-related disorders. This review will focus on the assessment of methodologies currently used for mitochondrial research and discuss their advantages, limitations and the implications of mitochondrial dysfunction in cardiovascular disorders

Dendrobium officinale

Background. Dendrobium officinale (DO) Kimura et Migo is a precious Chinese herb that is considered beneficial for health due to its antioxidant and antidiabetes properties, and so on. In this research, we try to determine the preventive effect of DO on the early complications of STZ-induced diabetic rats. Methods. Type 1 diabetic rats were produced with a single intraperitoneal injection of STZ (50 mg/kg). DO (1 g/kg/day) was then orally administered for 5 weeks. Blood glucose, TC, TG, BUN, CREA, and GSH-PX levels were determined, and electroretinographic activity and hypoalgesia were investigated. Pathological sections of the eyes, hearts, aortas, kidneys, and livers were analyzed. Results. Treatment with DO significantly attenuated the serum levels of TC, TG, BUN, and CREA, markedly increased the amplitudes of ERG a- and b-waves and Ops, and reduced the hypoalgesia and histopathological changes of vital organs induced by hyperglycemia. The protective effect of DO in diabetic rats may be associated with its antioxidant activity, as evidenced by the marked increase in the serum level of glutathione peroxidase. However, DO had no significant effect on blood glucose levels and bodyweight of diabetic rats. Conclusions. DO supplementation is an effective treatment to prevent STZ-induced diabetic complications

滨螺卓越的耐高温能力，温度耐受上限竟高达55℃——潮间带 Echinolittorina 属滨螺细胞质苹果酸脱氢酶高温耐受机制的研究

研究团队以分布于高潮间带，具有高耐热性的两种滨螺为研究对象，通过生理生化学实验及计算机模拟手段，发现耐热的软体动物通过增强代谢关键酶的作用，避免了在高温条件下的解链；研究团队还提出，局部柔性的增长使得酶在低温条件下能够发挥其催化功能，同时能在极端高温条件下，起到稳定蛋白质的作用，确保了蛋白质功能的维持。这些发现对于查明环境温度对生物分布的影响及其机制，预测气候变暖的生态学效应将具有重要意义。 滨螺广泛分布于潮间带高潮区，是潮间带垂直分布区划分的标志性物种。塔结节滨螺（Echinolittorina malaccana）和粒结节滨螺（E. radiata）是我国岩相潮间带高潮区常见物种，其温度耐受上限高达 55-60°C。董云伟教授团队与美国斯坦福大学 George Somero 教授，以及华侨大学张光亚教授团队合作，进行了一系列研究，探索了高热耐受性滨螺在极端高温条件下，仍旧保持体内蛋白质微结构的完整、功能的维持的奥妙所在。【Abstract】Snails of the genus Echinolittorina are among the most heat-tolerant animals; they experience average body temperatures near 41–44℃ in summer and withstand temperatures up to at least 55℃. Here, we demonstrate that heat stability of function (indexed by the Michaelis–Menten constant of the cofactor NADH, KMNADH) and structure (indexed by rate of denaturation) of cytosolic malate dehydrogenases (cMDHs) of two congeners (E. malaccana and E. radiata) exceeds values previously found for orthologs of this protein from less thermophilic species. The ortholog of E. malaccana is more heat stable than that of E. radiata, in keeping with the congeners' thermal environments. Only two inter-congener differences in amino acid sequence in these 332 residue proteins were identified. In both cases (positions 48 and 114), a glycine in the E. malaccana ortholog is replaced by a serine in the E. radiata protein. To explore the relationship between structure and function and to characterize how amino acid substitutions alter stability of different regions of the enzyme, we used molecular dynamics simulation methods. These computational methods allow determination of thermal effects on fine-scale movements of protein components, for example, by estimating the root mean square deviation in atom position over time and the root mean square fluctuation for individual residues. The minor changes in amino acid sequence favor temperature-adaptive change in flexibility of regions in and around the active sites. Interspecific differences in effects of temperature on fine-scale protein movements are consistent with the differences in thermal effects on binding and rates of heat denaturation.This research was substantially supported by grants from National Natural Science Foundation of China (41476115), Program for New Century Excellent Talents of Ministry of Education, China, Nature Science Foundation for Distinguished Young Scholars of Fujian Province (2017J07003), China and the State Key Laboratory of Marine Environmental Science Internal Program, Xiamen University (MELRI1501)

Serotonin receptor HTR6-mediated mTORC1 signaling regulates dietary restriction-induced memory enhancement

Dietary restriction (DR; sometimes called calorie restriction) has profound beneficial effects on physiological, psychological, and behavioral outcomes in animals and in humans. We have explored the molecular mechanism of DR-induced memory enhancement and demonstrate that dietary tryptophan-a precursor amino acid for serotonin biosynthesis in the brain-and serotonin receptor 5-hydroxytryptamine receptor 6 (HTR6) are crucial in mediating this process. We show that HTR6 inactivation diminishes DR-induced neurological alterations, including reduced dendritic complexity, increased spine density, and enhanced long-term potentiation (LTP) in hippocampal neurons. Moreover, we find that HTR6-mediated mechanistic target of rapamycin complex 1 (mTORC1) signaling is involved in DR-induced memory improvement. Our results suggest that the HTR6-mediated mTORC1 pathway may function as a nutrient sensor in hippocampal neurons to couple memory performance to dietary intake

Visfatin enhances breast cancer progression through CXCL1 induction in tumor-associated macrophages

Visfatin, an adipocytokine highly expressed in breast tumor tissues, is associated with breast cancer progression. Recent studies showed that adipocytokines mediate tumor development through adipocytokine tumor-stromal interactions in the tumor microenvironment. This study focused on the interaction between one key stromal constituent—tumor-associated macrophages—and visfatin. Pretreatment of THP-1 and peripheral blood mononuclear cells (PBMCs) with recombinant visfatin resulted in M2-polarization determined by CD163 and CD206 expression. Indirect co-culture with visfatin-treated THP-1 (V-THP-1) promoted the viability, migration, tumorsphere formation, EMT, and stemness of breast cancer cells. Cytokine array identified an increased CXCL1 secretion in V-THP-1 conditioned medium and recombinant CXCL1 enhanced cell migration and invasion, which were abrogated by the CXCL1-neutralizing antibody. Additionally, visfatin induced pERK in THP-1 cells and clinical samples confirmed a positive CXCL1/pERK correlation. In an orthotopic mouse model, the tumor bioluminescent signal of luciferase-expressing MDA-MB-231 (Luc-MDA-MB-231) cells co-cultured with V-THP-1 and the expression of proliferation marker Ki67 were significantly higher than that co-cultured with THP-1. Furthermore, tail vein-injected Luc-MDA-MB-231 pretreated with V-PBMCs conditioned medium metastasized to lungs more frequently compared to control, and this was reversed by CXCL1 blocking antibody. In summary, this study demonstrated that visfatin enhanced breast cancer progression via pERK/CXCL1 induction in macrophages

ADSCs stimulated by resistin promote breast cancer cell malignancy via CXCL5 in a breast cancer coculture model

The tumor microenvironment represents one of the main obstacles in breast cancer treatment owing to the presence of heterogeneous stromal cells, such as adipose-derived stem cells (ADSCs), that may interact with breast cancer cells and promote cancer development. Resistin is an adipocytokine associated with adverse breast cancer progression; however, its underlying mechanisms in the context of the breast tumor microenvironment remain largely unidentified. Here, we utilized a transwell co-culture model containing patient-derived ADSCs and breast cancer cell lines to investigate their potential interaction, and observed that breast cancer cells co-cultured with resistin-treated ADSCs (R-ADSCs) showed enhanced cancer cell growth and metastatic ability. Screening by proteome arrays revealed that C-X-C motif chemokine ligand 5 (CXCL5) was released in the conditioned medium of the co-culture system, and phosphorylated ERK was increased in breast cancer cells after co-culture with R-ADSCs. Breast cancer cells treated with the recombinant proteins of CXCL5 showed similarly enhanced cell migration and invasion ability as occurred in the co-culture model, whereas application of neutralizing antibodies against CXCL5 reversed these phenomena. The orthotopic xenograft in mice by breast cancer cells after co-culture with R-ADSCs had a larger tumor growth and more CXCL5 expression than control. In addition, clinical analysis revealed a positive correlation between the expression of resistin and CXCL5 in both tumor tissues and serum specimens of breast cancer patients. The current study suggests that resistin-stimulated ADSCs may interact with breast cancer cells in the tumor microenvironment via CXCL5 secretion, leading to breast cancer cell malignancy

MRE11 promotes oral cancer progression through RUNX2/CXCR4/AKT/FOXA2 signaling in a nuclease-independent manner

MRE11, the nuclease component of RAD50/MRE11/NBS1 DNA repair complex which is essential for repair of DNA double-strand-breaks in normal cells, has recently garnered attention as a critical factor in solid tumor development. Herein we report the crucial role of MRE11 in oral cancer progression in a nuclease-independent manner and delineate its key downstream effectors including CXCR4. MRE11 expression in oral cancer samples was positively associated with tumor size, cancer stage and lymph node metastasis, and was predictive of poorer patient survival and radiotherapy resistance. MRE11 promoted cell proliferation/migration/invasion in a nuclease-independent manner but enhanced radioresistance via a nuclease-dependent pathway. The nuclease independent promotion of EMT and metastasis was mediated by RUNX2, CXCR4, AKT, and FOXA2, while CXCR4 neutralizing antibody mitigated these effects in vitro and in vivo. Collectively, MRE11 may serve as a crucial prognostic factor and therapeutic target in oral cancer, displaying dual nuclease dependent and independent roles that permit separate targeting of tumor vulnerabilities in oral cancer treatment