Serum Anti-Fumarate Hydratase Autoantibody as a Biomarker for Predicting Prognosis of Acute-on-Chronic Liver Failure

Wei Linlin,Wang Ting,Chen Sisi,Liu Yeying,Huang Xueying,Zheng Sujun,Xu Bin,Ren Feng,Liu Mei 거트앤리버 소화기연관학회협의회 2023 Gut and Liver Vol.17 No.5

Background/Aims: To investigate the autoantibody against fumarate hydratase (FH), which is a specific liver failure-associated antigen (LFAA) and determine whether it can be used as a biomarker to evaluate the prognosis of acute-on-chronic liver failure (ACLF). Methods: An immunoproteomic approach was applied to screen specific LFAAs related to differential prognosis of ACLF (n=60). Enzyme-linked immunosorbent assay (ELISA) technology was employed for the validation of the frequency and titer of autoantibodies against FH in ACLF patients with different prognoses (n=82). Moreover, we clarified the expression of autoantibodies against FH in patients with chronic hepatitis B (n=60) and hepatitis B virus-related liver cirrhosis (n=60). The dynamic changes in the titers of autoantibodies against FH were analyzed by sample collection at multiple time points during the clinical course of eight ACLF patients with different prognoses. Results: Ultimately, 15 LFAAs were screened and identified by the immunoproteomic approach. Based on ELISA-based verification, anti-FH/Fumarate hydratase protein autoantibody was chosen to verify its expression in ACLF patients. ACLF patients had a much higher anti-FH autoantibody frequency (76.8%) than patients with liver cirrhosis (10%, p=0.000), patients with chronic hepatitis B (6.7%, p=0.022), and normal humans (0%, p=0.000). More importantly, the frequency and titer of anti-FH protein autoantibodies in the serum of ACLF patients with a good prognosis were much higher than that of patients with a poor prognosis (83.9% vs 61.5%, p=0.019; 1.41±0.85 vs 0.94±0.56, p=0.017, respectively). The titer of anti-FH autoantibodies showed dynamic changes in the clinical course of ACLF. Conclusions: The anti-FH autoantibody in serum may be a potential biomarker for predicting the prognosis of ACLF.

Dual delivery of bone morphogenetic protein‑2 and basic fibroblast growth factor from nanohydroxyapatite/collagen for bone tissue engineering

Yuqian Hu,Linlin Zheng,Jinhui Zhang,Lijuan Lin,Yue Shen,Xiaoyan Zhang,Buling Wu 한국응용생명화학회 2019 Applied Biological Chemistry (Appl Biol Chem) Vol.62 No.5

Background: In bone tissue engineering, the fabrication and biocompatibility of scaffold are crucial. Among many scaffold materials, nanohydroxyapatite (nHAP) and collagen (COL) are chosen as building materials of scaffold. At the same time, growth factors were also used to modify the scaffolds. Methods: In this study, blending and freeze drying methods were adopted together in order to build basic fibroblast growth factor (bFGF)-bone morphogenetic protein-2 (BMP-2)-nHAP/COL scaffolds. ELISA was applied to test the release of bFGF and BMP-2 on the scaffold. The flow cytometry was used to identify bone marrow mesenchymal stem cells (BMSCs). Scanning electron microscope was adopted to observe scaffolds and cells morphology. BMSCs were seeded on the scaffolds to test the biological compatibility in vitro. Cells were counted to detect early cell adhesion. Cell counting kit-8 assay was adopted to detect cell proliferation and alkalinephosphatase assay was applied to detect cell activity. Results: The characterization of bFGF-BMP-2-nHAP/COL scaffolds meets the requirements of ideal bone tissue engineering scaffolds. BMSCs that were isolated, purified and passaged satisfied the needs of further experiments. The growth status of cells on bFGF-BMP-2-nHAP/COL scaffolds was satisfactory. Cell adhesion was the highest in the bFGF-BMP-2-nHAP/COL scaffolds group. The cell viability and ALP activity of bFGF-BMP-2-nHAP/COL scaffolds group were the highest. Conclusion: Taken together, bFGF-BMP-2-nHAP/COL scaffolds have good biocompatibility in vitro and promote adhesion, proliferation, differentiation of BMSCs.

UV-ARTP-DES compound mutagenesis breeding improves natamycin production of Streptomyces natalensis HW-2 and reveals transcriptional changes by RNA-seq

Jianrui Sun,Jinglan Li,Linlin Yao,Yingying Zheng,Jiang-Feng Yuan,Da-Hong Wang 한국식품과학회 2023 Food Science and Biotechnology Vol.32 No.3

Natamycin is widely used in food, medical and health, agriculture, and animal husbandry. In this study, Streptomyces natalensis HW-2 was used as the research object, and a mutant DES-26 with stable genetic characters was selected by UV-ARTP-DES compound mutation. The natamycin yield was 1.64 g/L, 86.36% higher than original strain. Differential expression genes were analyzed by transcriptomics, and results showed that 295 and 860 genes were significantly differentially expressed at fermentation for 48 h and 72 h. GO and KEGG analysis showed that compound mutagenesis had a significant impact on glycolysis, pentose phosphate, TCA cycle, fatty acid metabolism pathways, and several key enzyme genes in the pathways were up-regulated, and genes related to natamycin biosynthesis (pimB-pimI) and transcriptional regulator (pimR) were also up-regulated. qRT-PCR results confirmed that expression levels of these genes were consistent with transcriptional changes of RNA-Seq.

Research on Thermal Refocusing System of High-resolution Space Camera

Weiyan Li,Qunbo Lv,Jian Wei Wang,Na Zhao,Zheng Tan,Linlin Pei 한국광학회 2022 Current Optics and Photonics Vol.6 No.1

A high-resolution camera is a precise optical system. Its vibrations during transportation and launch, together with changes in temperature and gravity field in orbit, lead to different degrees of defocus of the camera. Thermal refocusing is one of the solutions to the problems related to in-orbit defocusing, but there are few relevant thermal refocusing mathematical models for systematic analysis and research. Therefore, to further research thermal refocusing systems by using the development of a high-resolution micro-nano satellite (CX6-02) super-resolution camera as an example, we established a thermal refocusing mathematical model based on the thermal elasticity theory on the basis of the secondary mirror position. The detailed design of the thermal refocusing system was carried out under the guidance of the mathematical model. Through optical–mechanical–thermal integration analysis and Zernike polynomial calculation, we found that the data error obtained was about 1%, and deformation in the secondary mirror surface conformed to the optical index, indicating the accuracy and reliability of the thermal refocusing mathematical model. In the final ground test, the thermal vacuum experimental verification data and in-orbit imaging results showed that the thermal refocusing system is consistent with the experimental data, and the performance is stable, which provides theoretical and technical support for the future development of a thermal refocusing space camera.

Pituitary P62 deficiency leads to female infertility by impairing luteinizing hormone production

Li Xing,Zhou Ling,Peng Guiliang,Liao Mingyu,Zhang Linlin,Hu Hua,Long Ling,Tang Xuefeng,Qu Hua,Shao Jiaqing,Zheng Hongting,Long Min 생화학분자생물학회 2021 Experimental and molecular medicine Vol.53 No.-

P62 is a protein adaptor for various metabolic processes. Mice that lack p62 develop adult-onset obesity. However, investigations on p62 in reproductive dysfunction are rare. In the present study, we explored the effect of p62 on the reproductive system. P62 deficiency-induced reproductive dysfunction occurred at a young age (8 week old). Young systemic p62 knockout (p62 -/- ) and pituitary-specific p62 knockout (p62 flox/flox αGSU cre ) mice both presented a normal metabolic state, whereas they displayed infertility phenotypes (attenuated breeding success rates, impaired folliculogenesis and ovulation, etc.) with decreased luteinizing hormone (LH) expression and production. Consistently, in an infertility model of polycystic ovary syndrome (PCOS), pituitary p62 mRNA was positively correlated with LH levels. Mechanistically, p62 -/- pituitary RNA sequencing showed a significant downregulation of the mitochondrial oxidative phosphorylation (OXPHOS) pathway. In vitro experiments using the pituitary gonadotroph cell line LβT2 and siRNA/shRNA/plasmid confirmed that p62 modulated LH synthesis and secretion via mitochondrial OXPHOS function, especially Ndufa2, a component molecule of mitochondrial complex I, as verified by Seahorse and rescue tests. After screening OXPHOS markers, Ndufa2 was found to positively regulate LH production in LβT2 cells. Furthermore, the gonadotropin-releasing hormone (GnRH)-stimulating test in p62 flox/flox αGSU cre mice and LβT2 cells illustrated that p62 is a modulator of the GnRH-LH axis, which is dependent on intracellular calcium and ATP. These findings demonstrated that p62 deficiency in the pituitary impaired LH production via mitochondrial OXPHOS signaling and led to female infertility, thus providing the GnRH-p62-OXPHOS(Ndufa2)-Ca 2+ /ATP-LH pathway in gonadotropic cells as a new theoretical basis for investigating female reproductive dysfunction.