Transcription factor c-Rel regulated by E5 affects the whole process after HPV16 infection through miR-133a-modulated feedback loop aim at mir-379-369 cluster.

BACKGROUND: During the development of cervical cancer, HPV infection causes a series of changes in transcription factors and microRNAs. But their relationships with pathogenic processes are not clear. METHODS: Base on previous study, to analyse the relationship among HPV16 infection and the related transcription factors, related miRNAs, so as to further understand the molecular mechanism of HPV16 infection to cervical cancer, around the HPV16 related miRNAs we have reported, the methods of bioinformatics prediction, histology, cell model in vitro and molecular interaction were used for prediction and validation respectively RESULTS: The results showed that NF-κB family members(c-Rel, p65 and p50) were identified as main HPV16rmiR-transcription factors. They have different expressive characteristics in cervical lesions and play tumorigenesis or progression roles in different periods of HPV16 infection. c-Rel, p65 and p50 act as mediators which link the HPV16 E5 and HPV16 related miRNAs. Among them, c-Rel affects the occurrence and progression of cervical cancer during whole HPV16 infection stage through miR133a-3p-modulated mir-379-369 cluster with a positive feedback way which targeted c-Rel itself and its positive regulator AKT3. CONCLUSION: So in the course of HPV16 infection, the E5, c-Rel, and miR-133a-3p form a positive feedback system which aim at mir-379-369 cluster for the whole process from HPV16 infection to cervical cancer.

Daphnetin attenuates LPS-induced osteolysis and RANKL mediated osteoclastogenesis through suppression of ERK and NFATc1 pathways.

Aseptic prosthetic loosening and periprosthetic infection resulting in inflammatory osteolysis is a leading complication of total joint arthroplasty (TJA). Excessive bone destruction around the bone and prosthesis interface plays a key role in the loosening prostheses leading to revision surgery. The bacterial endotoxins or implant-derived wear particles-induced inflammatory response is the major cause of the elevated osteoclast formation and activity. Thus, agents or compounds that can attenuate the inflammatory response and/or inhibit the elevated osteoclastogenesis and excessive bone resorption would provide a promising therapeutic avenue to prevent aseptic prosthetic loosening in TJA. Daphnetin (DAP), a natural coumarin derivative, is clinically used in Traditional Chinese Medicine for the treatment of rheumatoid arthritis due to its anti-inflammatory properties. In this study, we report for the first time that DAP could protect against lipopolysaccharide-induced inflammatory bone destruction in a murine calvarial osteolysis model in vivo. This protective effect of DAP can in part be attributed to its direct inhibitory effect on RANKL-induced osteoclast differentiation, fusion, and bone resorption in vitro. Biochemical analysis found that DAP inhibited the activation of the ERK and NFATc1 signaling cascades. Collectively, our findings suggest that DAP as a natural compound has potential for the treatment of inflammatory osteolysis.

Inhibition of FABP5 attenuates inflammatory bowel disease by modulating macrophage alternative activation.

Fatty acid binding protein 5 (FABP5) is an intracellular chaperone of fatty acid molecules that regulates lipid metabolism and cell growth. However, its role in intestinal inflammation remains enigmatic. Through examination of human tissue samples and single-cell data, we observed a significant upregulation of FABP5 within the mucosa of patients afflicted with ulcerative colitis (UC) and Crohn's disease (CD), predominantly localized in intestinal macrophages. Herein, we investigate the regulation of FABP5-IN-1, a FABP5 inhibitor, on various cells of the gut in an inflammatory environment. Our investigations confirmed that FABP5 ameliorates DSS-induced colitis in mice by impeding the differentiation of macrophages into M1 macrophages in vitro and in vivo. Furthermore, following FABP5-IN-1 intervention, we observed a notable restoration of intestinal goblet cells and tuft cells, even under inflammatory conditions. Additionally, FABP5-IN-1 exhibits a protective effect against DSS-induced colitis by promoting the polarization of macrophages towards the M2 phenotype in vivo. In summary, FABP5-IN-1 confers protection against DSS-induced acute colitis through a multifaceted approach, encompassing the reduction of inflammatory macrophage infiltration, macrophage polarization, regulating Th17/Treg cells to play an anti-inflammatory role in IBD. The implications for IBD are underscored by the comprehensive in vivo and in vitro experiments presented in this article, thereby positioning FABP5 as a promising and novel therapeutic target for the treatment of IBD.

Responses of mangrove (Kandelia obovata) growth, photosynthesis, and rhizosphere soil properties to microplastic pollution.

In this study, we used Kandelia obovata to explore the toxicities of three typical MPs in mangroves: polyethylene, polypropylene, and polyvinylchloride. MPs were mixed into soils at 5 % (w/w) for cultivation in mangrove tide-tank system. Plant growth and soil characteristics were determined after 12 months. The results showed that MPs multiply restricted root growth, leaf ionome, chlorophyll concentration, and photosynthetic efficiency, changed leaf photochemical efficiency and excited energy distribution. Polyethylene and polypropylene MPs with 150 µm sizes significantly reduced leaf and root biomass. As for soil properties, all MPs mainly reduced bulk density but improved porosity, with 600 µm polyethylene resulting in 1.4 g cm-3 bulk density and 55.1 % porosity. This study represent the first paper highlighting that MPs negatively affect mangrove plants by affecting plant growth, leaf ionome, and photosynthesis, which may be related with the changed soil properties, especially reduced bulk density and improved porosity.

Distribution, characteristics, and human exposure to microplastics in mangroves within the Guangdong-Hong Kong-Macao Greater Bay Area.

In this study, three mangroves in the Guangdong-Hong Kong-Macao Greater Bay Area- Qi'ao Island in Zhuhai, Nansha in Guangzhou, and Futian in Shenzhen-were selected for investigating the distribution of microplastics and their characteristics The average microplastic abundance in each descended in the order: Futian (1600 n/kg) > Nansha (1100 n/kg) > Qi'ao Island (440 n/kg), with values from the forest fringe being significantly higher than those in the forest interior. The microplastics were mainly fibers, 1-5 mm in size, and white/black in color; they consisted of polypropylene and polyethylene, with foam and polystyrene accounting for a high proportion in Nansha. The exposure of humans to microplastics in the Futian forest fringe reached 35.95 ng/d·kg; it was one order of magnitude higher than the exposures in Qi'ao Island and Nansha. Furthermore, ingestion accounted for approximately 74% of the total exposure to the human body, dermal contact constitutes 25%, and sediment inhalation accounted for less than 1%.

α-Tomatine, a novel early-stage autophagy inhibitor, inhibits autophagy to enhance apoptosis via Beclin-1 in Skov3 cells.

Targeting the autophagy process is considered to be a promising new strategy for drug treatment of ovarian cancer. α-Tomatine, a steroidal alkaloid extracted, is mainly isolated from leaves, roots and immature green tomatoes. α-Tomatine has biological activities such as anticancer, antioxidative and anti-inflammatory. The study aimed to explore the effects of α-tomatine on proliferation, apoptosis and autophagy and the underlying mechanisms in ovarian cancer Skov3 cells. After treatment with different concentrations of α-tomatine (0, 0.75, 1 and 1.5 µM) in Skov3 cells for 24 h, proliferation was determined by the CCK-8 assay, and apoptosis was detected by flow cytometric analysis. Autophagy in cells was determined by the number of fluorescent spots using confocal fluorescence microscopy after mRFP-GFP-LC3 transfection. The relationship between autophagy and apoptosis was proved by Beclin-1 overexpression. The protein expression levels were tested by western blotting. The results demonstrated that α-tomatine effectively repressed proliferation, exerted a proapoptotic effect and inhibited early-stage autophagy in Skov3 cells in a dose- and time-dependent manner. Additionally, Beclin-1 overexpression significantly suppressed α-tomatine-treated apoptosis in Skov3 cells, indicating that α-tomatine inhibits autophagy to induce apoptosis. We also found α-tomatine inhibited the protein expression levels of PI3K/Akt/mTOR signaling pathway. However, the autophagy inhibition of α-tomatine could be reversed obviously by Beclin-1 overexpression. Taken together, α-tomatine inhibited autophagy through Beclin-1. Our study suggests that α-tomatine, as a novel early-stage autophagy inhibitor, might be a potential drug for further treatment of ovarian cancer by inhibiting proliferation and promoting apoptosis.

The distribution, characteristics and ecological risks of microplastics in the mangroves of Southern China.

During the production, use and disposal of plastic products, microplastics (MPs) are dispersed into the surrounding environment and have inevitable impacts on mangrove ecosystems in estuaries and offshore areas. In the mangroves of Southern China, the systematic evaluation of the distribution, characteristics and ecological risks of MPs is lacking. In this study, surface sediments (0-5 cm depth) were collected from six representative mangroves in China to explore MP contamination and its associated ecological risk. Based on the results, MP concentrations of MPs in mangrove sediments were as follows: FT (2249 ±â€¯747 items/kg), ZJ (736 ±â€¯269 items/kg), DF (649 ±â€¯443 items/kg), DZG (431 ±â€¯170 items/kg), YX (424 ±â€¯127 items/kg), and FCG (227 ±â€¯173 items/kg). The higher MP concentration in the Futian mangrove was mainly related to inputs from the Pearl River, the third largest river in China. The predominant shape, colour, and size of MPs were fibrous, white-transparent, and 500-5000 µm, respectively. The main MP polymer types were polypropylene, polyethylene, and polystyrene. Degradation artefacts were present on surface of MPs as well as metallic and non-metallic elements. MPs concentration in mangrove sediments increased with increasing social-economic development of surrounding districts, which indicated the clear influence of anthropogenic activity on MP pollution in these mangroves. Furthermore, total organic carbon (TOC) and silt content were positively associated with MPs (P < 0.01), indicating a facilitatory role in deposition of MPs in mangroves. Based on a comprehensive evaluation using the potential ecological risk factor (Ei), potential ecological risk (RI), polymer risk index (H) and pollution load index (PLI), MPs were found to present ecological risks in these mangroves, with the highest risk occurring in the Futian mangrove.

Magnetic and luminescent properties of lanthanide coordination polymers with asymmetric biphenyl-3,2',5'-tricarboxylate.

Eight isostructural lanthanide coordination polymers [Ln(bptc)(phen)(H2O)]n (Ln = Dy for , Eu for , Tb for , Gd for , Sm for , Nd for , Yb for , Pr for ) were successfully prepared based on bridging asymmetric polycarboxylate ligand biphenyl-3,2',5'-tricarboxylic acid (H3bptc) and chelating 1,10-phenanthroline (phen) coligand. Single crystal X-ray analysis reveals that complexes have a (3,6)-connected CdI2-type coordination network consisting of paddle-wheel dimers [Ln2(CO2)4]. The magnetic and fluorescent properties of have been investigated. Significantly, the Dy(iii) complex behaves with slow relaxation of the magnetization, where the frequency-dependent out-of-phase signals are noticed.