甘草次酸保肝功效的通路作用机制

甘草的活性成分包括甘草甜素(glycyrrhizin,GL)和甘草次酸(glycyrrhetinic acid,GA),而GA是甘草中的主要生物活性成分,是GL的主要代谢产物,部分GL通过细菌在肠内代谢为GA。在许多以往的研究中已经证实其具有多种药理学效果,例如抗炎、抗过敏、抗致癌、抗损伤和抗氧化特性以及肝脏保护。最近的研究表明,GA可以降低逆转录因子、二氧化钛纳米粒子和环磷酰胺诱导的肝毒性,并且可以保护免受四氯化碳诱导的肝损伤。已报道的GA的保肝作用机制主要归因于诱导抗氧化剂防御,抑制炎症反应和细胞色素P450表达,本文将对GA在不同信号通路中发挥保肝作用进行综述。     

Functional importance of palmitoyl protein thioesterase 1 (PPT1) expression by Sertoli cells in mediating cholesterol metabolism and maintenance of sperm quality

Sertoli cells are a type of nurse cell in the seminiferous epithelium that are crucial for sustaining spermatogenesis by extending nutritional and energy support to the developing germ cells. Dysfunction of Sertoli cells could cause disordered spermatogenesis and reduced fertility in males. In this study, we focused on the expression and function of palmitoyl protein thioesterase 1 (PPT1), a lysosomal depalmitoylating enzyme, in Sertoli cells. Here, we show that PPT1 expression in Sertoli cells is responsive to cholesterol treatment and that specific knockout of Ppt1 in Sertoli cells causes male subfertility associated with poor sperm quality and a high ratio of sperm deformity. Specifically, Ppt1 deficiency leads to poor cell variably accompanied with abnormal lysosome accumulation and increased cholesterol levels in Sertoli cells. Further, Ppt1 deficiency results in poor adhesion of developing germ cells to Sertoli cells in the seminiferous epithelium, which is likely to be responsible for the reduced male fertility as a consequence of declines in sperm count and motility as well as a high incidence of sperm head deformity. In summary, PPT1 affects sperm quality and male fertility through regulating lysosomal function and cholesterol metabolism in Sertoli cells.     

Improved Production of Spores and Bioactive Metabolites from Bacillus amyloliquefaciens in Solid-state Fermentation by a Rapid Optimization Process

Probiotics and Antimicrobial Proteins - A dipicolonic acid fluorimetry assay was used instead of plate counting for the assessment of spore yields for enhanced optimization efficiency. The...     

Construction of a Model Culture System of Human Colonic Microbiota to Detect Decreased Lachnospiraceae Abundance and Butyrogenesis in the Feces of Ulcerative Colitis Patients

Compositional alteration of the gut microbiota is associated with ulcerative colitis (UC). Here, a model culture system is established for the in vitro human colonic microbiota of UC, which will be helpful for determining medical interventions. 16S ribosomal RNA sequencing confirms that UC models are successfully developed from fecal inoculum and retain the bacterial species biodiversity of UC feces. The UC models closely reproduce the microbial components and successfully preserve distinct clusters from the healthy subjects (HS), as observed in the feces. The relative abundance of bacteria belonging to the family Lachnospiraceae significantly decreases in the UC models compared to that in HS, as observed in the feces. The system detects significantly lower butyrogenesis in the UC models than that in HS, correlating with the decreased abundance of Lachnospiraceae. Interestingly, the relative abundance of Lachnospiraceae does not correlate with disease activity (defined as partial Mayo score), suggesting that Lachnospiraceae persists in UC patients at a decreased level, irrespective of the alteration in disease activity. Moreover, the system shows that administration of Clostridium butyricum MIYAIRI restores butyrogenesis in the UC model. Hence, the model detects deregulation in the intestinal environment in UC patients and may be useful for simulating the effect of probiotics.     

A novel case of autogamy and cleistogamy in Dendrobium wangliangii: A rare orchid distributed in the dry‐hot valley

Dendrobium wangliangii is an epiphytic orchid distributed in the Jinshajiang dry‐hot valley in Luquan County, Yunnan Province, China. Most Dendrobium spp. typically have a low fruit set, but this orchid shows a higher fruit set under natural conditions despite the lack of effective pollinators. The pollination biology of the critically endangered D. wangliangii was investigated in this study. A fruit set rate of 33.33 ± 4.71% was observed after bagging treatment in 2017 and a high fruit set rate (65.72 ± 4.44% in 2011; 50.79 ± 5.44% in 2017) was observed under natural conditions, indicating that D. wangliangii is characterized by spontaneous self‐pollination. The anther cap blocked the growing pollinium; thus, the pollinium slid down and reached the stigmatic cavity, leading to autogamous self‐pollination. Specifically, 51.50% of 162 unopened flowers (total 257 flowers) of this Dendrobium species under extreme water‐deficit conditions developed into fruits, suggesting the presence of cleistogamy in D. wangliangii. Here, cleistogamy may represent the primary mode of pollination for this orchid. Spontaneous self‐pollination and specific cleistogamous autogamy could represent major adaptions to the drought and pollinator‐scarce habitat in the Jinshajiang dry‐hot valley.     

Dissecting the pretransitional conformational changes in aminoacylase I thermal denaturation

Aminoacylase I (ACYI) catalyzes the stereospecific hydrolysis of L-acylamino acids and is generally assumed to be involved in the final step of the degradation of intracellular N-acetylated proteins. Apart from its crucial functions in intracellular amino acid metabolism, ACYI also has substantial commercial importance for the optical resolution of N-acylated DL-amino acids. As a zinc-dependent enzyme, ACYI is quite stable against heat-induced denaturation and can be regarded as a thermostable enzyme with an optimal temperature for activity of approximately 65 degrees C. In this research, the sequential events in ACYI thermal denaturation were investigated by a combination of spectroscopic methods and related resolution-enhancing techniques. Interestingly, the results from fluorescence and infrared (IR) spectroscopy clearly indicated that a pretransitional stage existed at temperatures from 50 degrees C to 66 degrees C. The thermal unfolding of ACYI might be a three-state process involving an aggregation-prone intermediate appearing at approximately 68 degrees C. The pretransitional structural changes involved the partial unfolding of the solvent-exposed beta-sheet structures and the transformation of about half of the Class I Trp fluorophores to Class II. Our results also suggested that the usage of resolution-enhancing techniques could provide valuable information of the step-wise unfolding of proteins.     

Sex chromosomes of basal placental mammals

Placental (eutherian) mammals are currently classified into four superordinal clades (Afrotheria, Xenarthra, Laurasiatheria and Supraprimates) of which one, the Afrotheria (a unique lineage of African origin), is generally considered to be basal. Therefore, Afrotheria provide a pivotal evolutionary link for studying fundamental differences between the sex chromosomes of human/mouse (both representatives of Supraprimates and the index species for studies of sex chromosomes) and those of the distantly related marsupials. In this study, we use female fibroblasts to investigate classical features of X chromosome inactivation including replication timing of the X chromosomes and Barr body formation. We also examine LINE-1 accumulation on the X chromosomes of representative afrotherians and look for evidence of a pseudoautosomal region (PAR). Our results demonstrate that asynchronous replication of the X chromosomes is common to Afrotheria, as with other mammals, and Barr body formation is observed across all Placentalia, suggesting that mechanisms controlling this evolved before their radiation. Finally, we provide evidence of a PAR (which marsupials lack) and demonstrate that LINE1 is accumulated on the afrotherian and xenarthran X, although this is probably not due to transposition events in a common ancestor, but rather ongoing selection to retain recently inserted LINE1 on the X.     

Structural differences in centromeric heterochromatin are spatially reconciled on fertilisation in the mouse zygote

In mammals, paternal and maternal pronuclei undergo profound chromatin reorganisation upon fertilisation. How these events are orchestrated within centromeric regions to ensure proper chromosome segregation in the following cellular divisions is unknown. In this study, we followed the dynamic unfolding of the centromeric regions, i.e. the centric and pericentric satellite repeats, by DNA fluorescent in situ hybridization (FISH) during the first cell cycle up to the two-cell stage. The distinct chromatin from female and male gametes both undergo rapid remodelling and reach a zygotic organisation in which the satellites occupy restricted spatial domains surrounding the nucleolar precursor body. A transition from this zygotic to a somatic cell-like organisation takes place during the two-cell stage. Using 3D immuno-FISH, we find that, whereas maternal pericentric regions are marked with H3K9me3, H4K20me3 and HP1β, paternal ones only showed HP1β marking. Thus, despite different chromatin features, male and female pronuclei organise their centromeric regions in the same way within the nuclei to align chromosomes on the metaphase plate and segregate them appropriately. Our findings highlight the importance of ensuring a proper centromere function while preserving the distinction of parental genome origin during the return to totipotency in the zygote. Electronic supplementary material The online version of this article (doi:) contains supplementary material, which is available to authorized users.     

Wnt/beta-catenin signaling has an essential role in the initiation of limb regeneration

Anuran (frog) tadpoles and urodeles (newts and salamanders) are the only vertebrates capable of fully regenerating amputated limbs. During the early stages of regeneration these amphibians form a "blastema", a group of mesenchymal progenitor cells that specifically directs the regrowth of the limb. We report that wnt-3a is expressed in the apical epithelium of regenerating Xenopus laevis limb buds, at the appropriate time and place to play a role during blastema formation. To test whether Wnt/beta-catenin signaling is required for limb regeneration, we created transgenic X. laevis tadpoles that express Dickkopf-1 (Dkk1), a specific inhibitor of Wnt/beta-catenin signaling, under the control of a heat-shock promoter. Heat-shock immediately before limb amputation or during early blastema formation blocked limb regeneration but did not affect the development of contralateral, un-amputated limb buds. When the transgenic tadpoles were heat-shocked following the formation of a blastema, however, they retained the ability to regenerate partial hindlimb structures. Furthermore, heat-shock induced Dkk1 blocked fgf-8 but not fgf-10 expression in the blastema. We conclude that Wnt/beta-catenin signaling has an essential role during the early stages of limb regeneration, but is not absolutely required after blastema formation.