Preclinical study of pachyman inducing ferroptosis against ovarian cancer: Biological targets and underlying mechanisms.

Ferroptosis has gained extreme purpose in targeting cancer treatment. Poria cocos Wolf, a traditional Chinese herb, has potential anticancer properties, but the action and mechanism against ovarian cancer remain undetailed. Pachyman (Poria cocos polysaccharides) refers to the pharmacologically bioactive ingredients rich in Poria cocos. This study aimed to identify the potent actions and the network mechanisms of pachyman against ovarian cancer through preclinical analysis. Online-accessible database or platform was employed to predict candidate genes and core targets associated with ferroptosis in pachyman against ovarian cancer. Enrichment analyses were used to characterize the functional action and signaling mechanism in pachyman to treat ovarian cancer. Molecular docking imitation was conducted for verification of core target proteins. Network analysis uncovered that there were 30 mutual and 13 core genes targeting ferroptosis in pachyman and/against ovarian cancer, and additional enrichment analysis characterized that these core genes may act synergistically through multiple biological processes and molecular pathways associated with ferroptosis, including anti-inflammatory action, immunoregulation, and microenvironment modulation. The strongest affinities in core target proteins between pachyman and sarcoma (SRC), signal transducer, and activator of transcription 3 (STAT3) were further validated using molecular docking method. In conclusion, pachyman may induce antiovarian cancer potentials via regulating ferroptosis-associated biological functions and pharmacological mechanisms based on current bioinformatics findings. We reason that pachyman, the beneficial nutraceuticals, may be used clinically for future application in ovarian cancer treatment.

Ferroptosis-related biotargets and network mechanisms of fucoidan against colorectal cancer: An integrated bioinformatic and experimental approach.

Ferroptosis, a type of iron-dependent cell death, has been linked with the occurrence and progression of malignant tumors, including colorectal cancer (CRC). Fucoidan, an algal fucose-rich molecule, has been discovered preclinically to have an anti-CRC signature. Although some underlying mechanisms are reported, many signaling pathways associated with ferroptosis in fucoidan treatment of CRC are still unidentified. In this study, we applied network pharmacology and molecular docking technologies to unmask and identify the medication targets and pharmaceutical mechanisms involved in ferroptosis in fucoidan-treated CRC. 19 ferroptosis-related core targets were identified and enrichment analysis indicated their contribution to pharmacological actions and mechanisms in fucoidan treatment of CRC, including ferroptosis-related signaling pathways. Additional molecular docking verification confirmed that fucoidan docked well with ranked core targets, including transcription factor p65 (RELA), interleukin-1 beta (IL1B), and interleukin-6 (IL6). These in silico findings were validated experimentally in CRC cells following fucoidan treatment. RELA, IL1B, and IL6 expressed positively in human CRC samples. In conclusion, the pharmacological mechanisms of fucoidan in treating CRC may be achieved through multiple biological targets and multiple molecular pathways associated with ferroptosis. Thus, these preclinical findings have laid a theoretical foundation for further research and clinical treatment of CRC using fucoidan.

Star Centroiding Based on Fast Gaussian Fitting for Star Sensors.

The most accurate star centroiding method for star sensors is the Gaussian fitting (GF) algorithm, because the intensity distribution of a star spot conforms to the Gaussian function, but the computational complexity of GF is too high for real-time applications. In this paper, we develop the fast Gaussian fitting method (FGF), which approximates the solution of the GF in a closed-form, thus significantly speeding up the GF algorithm. Based on the fast Gaussian fitting method, a novel star centroiding algorithm is proposed, which sequentially performs the FGF twice to calculate the star centroid: the first FGF step roughly calculates the Gaussian parameters of a star spot and the noise intensity of each pixel; subsequently the second FGF accurately calculates the star centroid utilizing the noise intensity provided in the first step. In this way, the proposed algorithm achieves both high accuracy and high efficiency. Both simulated star images and star sensor images are used to verify the performance of the algorithm. Experimental results show that the accuracy of the proposed algorithm is almost the same as the GF algorithm, higher than most existing centroiding algorithms, meanwhile, the proposed algorithm is about 15 times faster than the GF algorithm, making it suitable for real-time applications.

[Robustness analysis of adaptive neural network model based on spike timing-dependent plasticity].

To explore the self-organization robustness of the biological neural network, and thus to provide new ideas and methods for the electromagnetic bionic protection, we studied both the information transmission mechanism of neural network and spike timing-dependent plasticity (STDP) mechanism, and then investigated the relationship between synaptic plastic and adaptive characteristic of biology. Then a feedforward neural network with the Izhikevich model and the STDP mechanism was constructed, and the adaptive robust capacity of the network was analyzed. Simulation results showed that the neural network based on STDP mechanism had good rubustness capacity, and this characteristics is closely related to the STDP mechanisms. Based on this simulation work, the cell circuit with neurons and synaptic circuit which can simulate the information processing mechanisms of biological nervous system will be further built, then the electronic circuits with adaptive robustness will be designed based on the cell circuit.

[Construction of human TAP1 expression vector and the effects of it on HLA-I expression in GES-1 cells in vitro].

AIM: To construct the human TAP1 expression vector and to evaluate its effects on HLA-I expression in GES-1 cells in vitro. METHODS: The human TAP1 expression vector (pcDNA3.1/V5-His-TAP1) was constructed by gene recombination technology. The expression of HLA-I on human gastric epithelial cell line (GES-1 cells) after transfection was detected by RT-PCR, Western blot and flow cytometry (FCM). RESULTS: Human full-length TAP1 gene was obtained from human peripheral blood mononuclear cells by RT-PCR reaction, then TAP1 gene was inserted into pcDNA3.1/V5-HisB vector to get the TAP1 expression vector (pcDNA3.1/V5-His-TAP1) by recombination technology including digestion with restriction enzymes, ligation and transformation. The vector was sequenced to ensure the sequence fidelity.To further evaluate the function of the TAP1 plasmid we constructed, GES-1 cells were selected as the target cell to be transfected. Firstly RT-PCR and Western blot results showed that the expression of TAP in GES-1 cells was increased after pcDNA3.1/V5-His-TAP1 transfection. Based on the high efficiency of transfection in GES-1 cell, we then detected the expression of HLA-I. The results showed that the expressions of HLA-A, HLA-B and HLA-C at mRNA level were all increased by TAP1 transfection, but no change was found in beta2m mRNA. HLA-I protein level was increased correspondingly with the TAP expression in cells by FCM and Western blot assay. CONCLUSION: The TAP1 expression vector was successfully constructed, and it can induce the expression of HLA-I on the GES-1 cells after TAP1 transfection. The results confirm that the TAP1 plays a cruical role in the HLA-I antigen expression and antigen presentation pathway.

[The research on the law of greenhouse gases emission from warm temperate forest soils in Beijing region].

In situ measurements by closed chamber technique were done to investigate the law of greenhouse gases (Methane, carbon dioxide and Nitrous Oxide) fluxes emission from different warm temperate forest soils (Broad-leaved forest, Form. Quercus liaotungensis and Form. Pinus tabulae) of Dongling mountain in Beijing region. Results show that the all representative types forest soils were sink of CH4 and source of CO2 and N2O. Different type of vegetables and soils result of different fluxes range of the main greenhouse gases. The fluxes range of CH4, CO2 and N2O emission from the three types forest soils were: 42-103 micrograms/(m2.h), 15-344 mg/(m2.h) and -61-101 micrograms/(m2.h); 13-182 micrograms CH4/m2.h, 23-380 mg/(m2.h) and -15-183 micrograms/(m2.h); 12-128 ug CH4/m2.h, 15-292 mg/(m2.h) and -94-153 micrograms/(m2.h); respectively. The mean fluxes of CH4, CO2 and N2O emission from the three types forest soils during the observation period were: -66 micrograms/(m2.h), 145 mg/(m2.h) and 22 micrograms/(m2.h); -67 micrograms/(m2.h), 146 mg/(m2.h) and 45 micrograms/(m2.h); -79 micrograms/(m2.h), 150 mg/(m2.h) and 31 micrograms/(m2.h), respectively. The total amounts of CH4 CO2 and N2O emission from the three types forest soils were -5.34 kg/(hm2.a), 13.9 Mg/(hm2.a) and 2.58 kg/(hm2.a); -6.20 kg/(hm2.a), 14.07 Mg/(hm2.a) and 4.19 kg/(hm2.a); -6.85 kg/(hm2.a), 15.71 Mg/(hm2.a) and 4.30 kg/(hm2.a), respectively.