FOXM1 (forkhead box protein M1) is a critical proliferation-associated transcription factor that is widely spatiotemporally expressed during the cell cycle. It is closely involved with the processes ...of cell proliferation, self-renewal, and tumorigenesis. In most human cancers, FOXM1 is overexpressed, and this indicates a poor prognosis for cancer patients. FOXM1 maintains cancer hallmarks by regulating the expression of target genes at the transcriptional level. Due to its potential role as molecular target in cancer therapy, FOXM1 was named the Molecule of the Year in 2010. However, the mechanism of FOXM1 dysregulation remains indistinct. A comprehensive understanding of FOXM1 regulation will provide novel insight for cancer and other diseases in which FOXM1 plays a major role. Here, we summarize the transcriptional regulation, post-transcriptional regulation and post-translational modifications of FOXM1, which will provide extremely important implications for novel strategies targeting FOXM1.
Aberrant expression of circular RNAs contributes to the initiation and progression of cancers, but the underlying mechanism remains elusive.
RNA-seq and qRT-PCR were performed to screen differential ...expressed circRNAs between gastric cancer tissues and adjacent normal tissues. Candidate circRNA (circMRPS35) was screened out and validated by qRT-PCR. Cell proliferation and invasion ability were determined by CCK-8 and cell invasion assays. RNA-seq, GO-pathway, RNA pull-down and ChIRP were further applied to search for detailed mechanism.
Here, a novel circRNA named circMRPS35, was screened out by RNA-seq in gastric cancer tissues, whose expression is related to clinicopathological characteristics and prognosis in gastric cancer patients. Biologically, circMRPS35 suppresses the proliferation and invasion of gastric cancer cells in vitro and in vivo. Mechanistically, circMRPS35 acts as a modular scaffold to recruit histone acetyltransferase KAT7 to the promoters of FOXO1 and FOXO3a genes, which elicits acetylation of H4K5 in their promoters. Particularly, circMRPS35 specifically binds to FOXO1/3a promoter regions directly. Thus, it dramatically activates the transcription of FOXO1/3a and triggers subsequent response of their downstream target genes expression, including p21, p27, Twist1 and E-cadherin, resulting in the inhibition of cell proliferation and invasion. Moreover, circMRPS35 expression positively correlates with that of FOXO1/3a in gastric cancer tissues.
Our findings not only reveal the pivotal roles of circMRPS35 in governing histone modification in anticancer treatment, but also advocate for triggering circMRPS35/KAT7/FOXO1/3a pathway to combat gastric cancer.
The endoglycosidase heparanase which degrades heparan sulfate proteoglycans, exerts a pro-inflammatory mediator in various inflammatory disorders. However, the function and underlying mechanism of ...heparanase in acute pancreatitis remain poorly understood. Here, we investigated the interplay between heparanase and the gut microbiota in the development of acute pancreatitis.
Acute pancreatitis was induced in wild-type and heparanase-transgenic mice by administration of caerulein. The differences in gut microbiota were analyzed by 16S ribosomal RNA sequencing. Antibiotic cocktail experiment, fecal microbiota transplantation, and cohousing experiments were used to assess the role of gut microbiota.
As compared with wild-type mice, acute pancreatitis was exacerbated in heparanase-transgenic mice. Moreover, the gut microbiota differed between heparanase-transgenic and wild-type mice. Heparanase exacerbated acute pancreatitis in a gut microbiota-dependent manner. Specially, the commensal Parabacteroides contributed most to distinguish the differences between wild-type and heparanase-transgenic mice. Administration of Parabacteroides alleviated acute pancreatitis in wild-type and heparanase-transgenic mice. In addition, Parabacteroides produced acetate to alleviate heparanase-exacerbated acute pancreatitis through reducing neutrophil infiltration.
The gut-pancreas axis played an important role in the development of acute pancreatitis and the acetate produced by Parabacteroides may be beneficial for acute pancreatitis treatment. Video abstract.
Immune response plays a vital role in the pathogenesis of neuropathic pain. Immune response-targeted therapy becomes an effective strategy for treating neuropathic pain. Licochalcone A (Lic-A) ...possesses anti-inflammatory and neuroprotective effects. However, the potential of Lic-A to attenuate neuropathic pain has not been well explored. To investigate the protective effect and evaluate the underlying mechanism of Lic-A against neuropathic pain in a rat model. Chronic constriction injury (CCI) surgery was employed in rats to establish neuropathic pain model. Rats were intraperitoneally administrated with Lic-A (1.25, 2.50 and 5.00 mg/kg) twice daily. Mechanical withdrawal threshold and thermal withdrawal latency were used to evaluate neuropathic pain. After administration, the lumbar spinal cord enlargement of rats was collected for ELISA, Western blot and immunofluorescence analysis. Mechanical withdrawal threshold and thermal withdrawal latency results showed that Lic-A significantly attenuated CCI-evoked neuropathic pain in dose-dependent manner. Lic-A administration also effectively blocked microglia activation. Moreover, Lic-A suppressed p38 phosphorylation and the release of inflammatory factors such as tumor necrosis factor-α, interleukin-1 and interleukin-6. Our findings provide evidence that Lic-A may have the potential to attenuate CCI-evoked neuropathic pain in rats by inhibiting microglia activation and inflammatory response.
This study aimed to modify an electrospun regenerated cellulose (RC) nanofiber membrane by surface grafting 2-(dimethylamino) ethyl methacrylate (DMAEMA) as a monomer via atom transfer radical ...polymerization (ATRP), as well as investigate the effects of ATRP conditions (i.e., initiation and polymerization) on enzyme immobilization. Various characterizations including XPS, FTIR spectra, and SEM images of nanofiber membranes before and after monomer grafting verified that poly (DMAEMA) chains/brushes were successfully grafted onto the RC nanofiber membrane. The effect of different ATRP conditions on laccase immobilization was investigated, and the results indicated that the optimal initiation and monomer grafting times were 1 and 2 h, respectively. The highest immobilization amount was obtained from the RC-Br-1h-poly (DMAEMA)-2h membrane (95.04 ± 4.35 mg), which increased by approximately 3.3 times compared to the initial RC membrane (28.57 ± 3.95 mg). All the results suggested that the optimization of initiation and polymerization conditions is a key factor that affects the enzyme immobilization amount, and the surface modification of the RC membrane by ATRP is a promising approach to develop an advanced enzyme carrier with a high enzyme loading capacity.
A member of the interleukin (IL)-1 superfamily was IL-36, which contained IL-36α, IL-36β, IL-36γ, and IL-36Ra. Heterotrimer complexes, consisting of heterodimeric receptor complexes and IL-36 ...agonist, gave signals through intracellular functional domains, so as to bind to downstream proteins and induce inflammatory response. IL-36 agonists upregulated mature-associated CD80, CD86, MHCII, and inductively produced several pro-inflammatory cytokines through the IL-36R-dependent manner in dendritic cells (DCs). Besides, DCs had the ability to initiate the differentiation of helper T (Th) cells. Up to date, the role of IL-36 in immunity, inflammation and other diseases is of great importance. Additionally, autoimmune diseases were characterized by excessive immune response, resulting in damage and dysfunction of specific or multiple organs and tissues. Most autoimmune diseases were related to inflammatory response. In this review, we will conclude the recent research advances of IL-36 in the occurrence and development of autoimmune diseases, which may provide new insight for the future research and the treatment of these diseases.
Almost all the commercial fishery stocks have been overexploited, resulting in dramatic populations decline and phenotypic change. Understanding the genetic effects of overexploitation have important ...implications for the conservation and management of fishery resources. In the present study, we investigated temporal changes of genetic diversity and spatio-temporal genetic structure in the heavily exploited large yellow croaker (
Larimichthys crocea
) in the East China Sea, through microsatellite analysis of historical and contemporary samples. Despite the drastic population decline, we found no significant decline in measures of genetic diversity (
Ar
,
He
and
F
IS
). The contemporary effective population sizes were still large enough and genetic drift was not strong enough to reduce the genetic diversity of large yellow croaker significantly in the East China Sea. Furthermore, no evidence of spatio-temporal genetic structure was detected. All the analysis of genetic structure indicated that the proportion of variance explained by temporal factors was small and similar with that of spatial factors. We therefore concluded that the genetic structure of the large yellow croaker in the East China Sea has been essentially stable over the time-span of 60 years. These results suggested that the drastic population declines did not change genetic composition of large yellow croaker in the East China Sea. Based on the long-term stable temporal pattern of genetic composition, we suggested that fishing restrictions and habitat restoration should be the most direct and effective management strategy for the recovery of large yellow croaker stocks.
Abstract
Sharing economy offers an alternative to customers with on‐demand services and opens up a new way for owners of underutilized resources to generate revenue. However, there is little evidence ...on whether sharing economy benefits the community of customers and suppliers or not. Our work is motivated by the ongoing stories of conflicts related to the ride sharing platforms (e.g., Uber, Lyft) and the information we collected from industry practitioners. We propose an economic model that describes how a price manipulating ride sharing platform crowdsources and matches supply to demand. Furthermore, our model captures how sharing economy's manipulative power impacts the community of customers and suppliers. Sharing economy platforms allow customers to make purchase decisions after evaluating the search cost, which depends on other customers' purchase decisions and leads to endogenous demand for sharing economy services. A comprehensive theoretical analysis of such models can be extremely challenging due to the endogenous demand. However, we provide such analysis by assuming that the customers evaluate the search cost with the estimated or “exogenous” demand instead of the realized or “endogenous” demand. Moreover, we support our theoretical findings in more realistic settings by performing various numerical analyses. Our results suggest that the financial objective of sharing economy may conflict with the welfare of the affected community, which can be mitigated by government regulations that impose upper bounds on price surges. Our work helps researchers, practitioners, and public policy makers more comprehensively understand the challenges that sharing economy brings and suggests possible regulatory intervention.
Via the empirical evidences from Airbnb from eight major cities in U.S., we examine the role of information disclosure in influencing consumers' purchase behavior on this sharing economy platform. We ...analyze information disclosure from four aspects – namely, what information (i.e., information content), from where (i.e., information source), in what format (information presentation format), and how much (the quantity of information). We find all three information sources – providers, platform, and peer consumers – influence consumer purchase behavior. Regarding information posted by providers, we find a concave relationship between room information (i.e. the number of photos and the length of description) and consumer purchase behavior. However, no significant relationship between providers' self-description (texts and photos) and consumer purchase behavior is found. Regarding information posted by platform, both the recommendation from platform and provider verification information positively influence consumer purchase behavior. For provider-consumer interactions information, the providers' high response rate and fast response speed enhance consumer purchase behavior. However, providing connections to providers' social media profiles negatively influences consumers' purchasing behavior. Regarding the information from peer consumers, we find although consumers' overall ratings positively affect consumer purchase behavior, such influence diminishes when the ratings exceed certain thresholds. Our study provides implications for platform owners to optimize information presentation layout directly through the platform design or indirectly through the guidance to the providers' information disclosure to facilitate consumers’ information search and acquisition to reduce the perceived risk, enhance trust on providers and the platform, and thus enhance their purchase intention and behavior.
•We collected 8804 Airbnb room listings from eight U.S. major cities to analyze.•We analyzed information disclosure through source, content, format, and quantity.•Information from providers, platform, and consumers affects purchase behavior.•Extra information may exhibit diminishing effect on customer purchase behavior.•We discuss implications for platform to optimize information presentation layout.
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