Influence of Gut Microbiota and its Metabolites on Progression of Metabolic Associated Fatty Liver Disease / 中国医学科学杂志(英文版)

Metabolic associated fatty liver disease (MAFLD) has become a prevalent chronic liver disease worldwide because of lifestyle and dietary changes. Gut microbiota and its metabolites have been shown to play a critical role in the pathogenesis of MAFLD. Understanding of the function of gut microbiota and its metabolites in MAFLD may help to elucidate pathological mechanisms, identify diagnostic markers, and develop drugs or probiotics for the treatment of MAFLD. Here we review the pathogenesis of MAFLD by gut microbiota and its metabolites and discuss the feasibility of treating MAFLD from the perspective of gut microbes.

Research Progress in Targeted Therapy of Hepatocellular Carcinoma / 中国医学科学杂志(英文版)

Hepatocellular carcinoma (HCC) is one of the most common malignancies, and its treatment is limited. With the understanding of key genes and signaling pathways in the occurrence and development of HCC, targeted drugs with high selectivity and low toxicity have been developed continuously, bringing a variety of options for the treatment of advanced HCC. In this article, the research progress on representative drugs of targeted therapy and potential therapeutic targets for HCC are reviewed.

Low Doses of Nonylphenol Promote Growth of Colon Cancer Cells through Activation of ERK1/2 via G Protein‒Coupled Receptor 30 / Journal of the Korean Cancer Association, 대한암학회지

PURPOSE: Nonylphenol (NP) is an endocrine disruptor found in products such as cleaners, plastics, and detergents. It exerts actions similar to endogenous 17β-estradiol (E2) and is reported to influence various cancers. However, its role in colon cancer remains elusive. MATERIALS AND METHODS: Colon cancer cell lines COLO 205 and SW480 were employed in our study. The cells were treated with NP or E2 followed by measurement of apoptosis and proliferation using flow cytometry and MTT assays, respectively. G protein–coupled estrogen receptor 30 (GPR30) expression was visualized using immunofluorescence and Western blot. To investigate the underlying mechanism, the expression levels of GPR30, p-protein kinase A (PKA), c-myc, cyclin D1, and ERK1/2 were analyzed using Western blot. Meanwhile, the GPR30 antagonist G15 was utilized to validate the role of GPR30 in colon cancer progression. Finally, the effect of a GPR30 inhibitor on tumor growth was determined in vivo using tumor xenograft mouse models. RESULTS: NP facilitated the proliferation of colon cancer cells and induced apoptosis failure in vitro. Western blot revealed increased GPR30 expression levels in response to NP treatment. Cyclin D1, p-PKA, c-myc, and proliferating cell nuclear antigen, proteins that regulate the cell cycle, were all upregulated by NP, and NP-mediated ERK1/2 activation and subsequent cell proliferation were abrogated by the GPR30 inhibitor G15. Moreover, colon cancer mice that received G15 administration demonstrated impaired tumor growth in vivo. CONCLUSION: Low dose NP promotes the growth of colon tumors through GPR30-mediated activation of ERK1/2 signaling.

Finite element analysis on simulation of change characteristics in human lumbar vertebrae under different motion status / 医用生物力学

Objective To compare characteristics of stress variations in 3D finite element models of normal and degenerative lumbar vertebrae and the dose-effect relationship, and analyze the mechanism of mechanical balance by traditional Chinese medicine (TCM) manipulation on degenerative lumbar vertebrae. Methods The 3D finite element model of intact, real human degenerative lumbar vertebrae (L4-5) was established to simulate the physiological activity of flexion and extension in lumbar vertebrae. The characteristics of stress variation in degenerative lumbar vertebrae under external loading, namely, the TCM manipulation was analyzed, and the stress variation in degenerative lumbar vertebrae under gradual increasing-external loading was analyzed as well, which was compared with the stress and strain variation in normal lumbar vertebrae under different motion status. Results Under different motion status, the stress distributions on lumbar disc as well as the elastic modulus of nucleus pulposus and fiber ring showed a gradually increasing tendency with lumbar degeneration increasing. TCM manipulation could change the stress distributions on lumbar disc, enlarge the space of spinal canal to a certain degree, and decrease the stress on nerve root. Stresses on small joints of the vertebral body and vertebral pedicle under posterior extension were larger than those under anterior flexion, while stresses on intervertebral disc under anterior flexion were greater than those under posterior extension, which showed a gradually increasing trend from top to bottom. Conclusions The mechanical environment of human lumbar vertebrae can be balanced by TCM manipulation, for the purpose of improving and treating lumbar disc diseases. The comparison with the 3D finite element model of normal human lumbar vertebrae and investigation on lumbar degeneration from perspective of changes in biomechanical environment and characteristics can provide scientific basis for clinic application of TCM manipulation in prevention and treatment of lumbar degenerative diseases, as well as new research idea for studying mechanical mechanism of TCM manipulation in effective prevention and treatment of lumbar lesions.

Roles of Long-chain Acyl Coenzyme A Synthetase in Absorption and Transport of Fatty Acid / 中国医学科学杂志(英文版)

Long-chain acyl coenzyme A synthetase (ACSL) is a member of the synthetase family encoded by a multigene family; it plays an important role in the absorption and transport of fatty acid. Here we review the roles of ACSL in the regulating absorption and transport of fatty acid, as well as the connection between ACSL and some metabolic diseases.

Effect of Autophagy Over Liver Diseases / 中国医学科学杂志(英文版)

In recent years, increasingly evidences show that autophagy plays an important role in the pathogenesis and development of liver diseases, and the relationship between them has increasingly become a focus of concern. Autophagy refers to the process through which the impaired organelles, misfolded protein, and intruding microorganisms is degraded by lysosomes to maintain stability inside cells. This article states the effect of autophagy on liver diseases (hepatic fibrosis, fatty liver, viral hepatitis, and liver cancer), which aims to provide a new direction for the treatment of liver diseases.

Relation Between Cellular Senescence and Liver Diseases / 中国医学科学杂志(英文版)

Cellular senescence refers to a process that cellular proliferation and differentiation modulated by the multiple stimulating factors gradually decline. Aging cells present the irreversible stop of proliferation and differentiation and change in secretory function because the cell cycle of aging cells is steadily blocked at some point. It has have been shown that cellular senescence plays an important role in the occurrence and development of liver diseases. In this paper, we review the advances in relations between cellular senescence and liver diseases.

Progress of targeting transforming growth factor-β1 small interfering RNA in liver fibrosis / 中国医学科学杂志(英文版)

Liver fibrosis is a common pathological consequence of a variety of chronic stimuli, including viral, autoimmune, drug-induced, cholestatic and metabolic diseases. Fibrosis is driven by a dynamic process involving increased synthesis of matrix components and a failure of physiological mechanisms of matrix turnover. Activation of hepatic stellate cells (HSCs) remains a central event in fibrosis. HSCs are the main source of extracellular matrix (ECM). Transforming growth factor-beta (TGF-Β), which is the fibrogenic master cytokine, can induce the activation of HSCs to produce a large amount of ECM, and is capable of inducing apoptosis of liver cells. RNA interference (RNAi) is a novel gene disruption technology. Studies have shown that small interfering RNA (siRNA) targeting TGF-Β1 may inhibit the activation and proliferation of HSCs, suppress ECM synthesis and block liver fibrosis. TGF-Β1 siRNA-mediated gene silencing therapy provides a new avenue for liver fibrosis. This review summarizes recent progresses in research on HSCs, TGF-Β1 and TGF-Β1 siRNA in liver fibrosis.

Roles of the lipid metabolism in hepatic stellate cells activation △ / 中国医学科学杂志(英文版)

The lipids present in hepatic stellate cells (HSCs) lipid droplets include retinyl ester, triglyceride, cholesteryl ester, cholesterol, phospholipids and free fatty acids. Activation of HSCs is crucial to the development of fibrosis in liver disease. During activation, HSCs transform into myofibroblasts with concomitant loss of their lipid droplets and production of excessive extracellular matrix. Release of lipid droplets containing retinyl esters and triglyceride is a defining feature of activated HSCs. Accumulating evidence supports the proposal that recovering the accumulation of lipids would inhibit the activation of HSCs. In healthy liver, quiescent HSCs store 80% of total liver retinols and release them depending on the extracellular retinol status. However, in injured liver activated HSCs lose their retinols and produce a considerable amount of extracellular matrix, subsequently leading to liver fibrosis. Further findings prove that lipid metabolism of HSCs is closely associated with its activation, yet relationship between activated HSCs and the lipid metabolism has remained mysterious.

Intervention of selenium on neurogranin expression in filial cerebrum of mice with excess iodine / 中华预防医学杂志

<p><b>OBJECTIVE</b>To study the effects of excess iodine intake on neurogranin expression in cerebrum of filial mice and the intervention of selenium.</p><p><b>METHODS</b>Sixty BALB/c mice were divided randomly into four groups with different drinking water: control group (tap water, NC), excess iodine group (3000 microg/L I, EL +), supplementing selenium group (200 microg/L Se, Se +) and the excess iodine plus selenium (3000 microg/L + I 200 microg/L Se, EI + Se +) group. The mice were mated at the end of the fourth month. Serum T4 and T3 were determined on postnatal day 14 and 28. The expression level of neurogranin in filial cerebrum was measured by immunohistochemistry and Western blot.</p><p><b>RESULTS</b>Serum T4 level in EI (68.78 +/- 11.10 nmol/ L) + was lower significantly than that in NC (100.85 +/- 11.47 nmol/ L) and EI + Se + (93.15 +/- 12.10 nmol/ L) on postnatal day 14. Western blot analysis showed that the relative level of neurogranin in EI + (0.621 +/- 0.041) was lower than that in NC (0.841 +/- 0.039) and EI + Se + (0.781 +/- 0.029) on postnatal day 14 (P < 0.05). No significant difference in serum T4 and neurogranin level between four groups on postnatal day 28.</p><p><b>CONCLUSION</b>Excess iodine intake might change the expression of neurogranin in filial cerebrum and the selenium supplementation might alleviate it.</p>

Effect of selenium supplementation on activity and mRNA expression of type 1 deiodinase in mice with excessive iodine intake / 生物医学与环境科学（英文）

<p><b>OBJECTIVE</b>To investigate the effect of selenium supplementation on the selenium status and selenoenzyme, especially the activity and mRNA expression of type 1 deiodinase (D1) in mice with excessive iodine (EI) intake and to explore the mechanism of selenium intervention on iodine-induced abnormities.</p><p><b>METHODS</b>Weanling female BALB/c mice were given tap water or 3 mg/L of iodine or supplemented with 0.5 mg/L or 1.0 mg/L of selenium in the presence of excessive iodine for 5 months. Selenium status, thyroid hormone level, hepatic and renal D1 activity and mRNA expression were examined.</p><p><b>RESULTS</b>Excessive iodine intake significantly decreased the selenium concentration in urine and liver, and the activity of glutathione peroxidase (GSH-Px) in liver. Meanwhile, serum total T4 (TT4) increased while serum total T3 (TT3) decreased. Hepatic D1 enzyme activity and mRNA expression were reduced by 33% and 86%, respectively. Renal D1 enzyme activity and mRNA were reduced by 30% and 55%, respectively. Selenium supplementation obviously increased selenium concentration, activity of GSH-Px and Dl as well as mRNA expression of D1. However, increasing the supplementation of Se from 0.5 to 1.0 mg/L did not further increase selenoenzyme activity and expression.</p><p><b>CONCLUSION</b>Relative selenium deficiency caused by excessive iodine plays an essential role in the mechanism of iodine-induced abnormalities. An appropriate dose of selenium supplementation exercises a beneficial intervention.</p>

Effects of long-term excessive Iodine intake on the maternal-fetal thyroid hormone metabolism in mice / 中华内分泌代谢杂志

Long-term excessive iodine intake resulted in an increased TT_4 level and a decreased TT_3 level in maternal serum,meanwhile,hepatic and renal type 1 deiodinase activity decreased dose-dependently.A significant reduction in type 2 deiodinase ( D2 ) activity of 12.5 d placenta was found in 3.0 mg/L or above groups.For 19.5 d uterus,D2 activity decreased and type 3 deiodinase activity increased.The results suggest that excessive iodine has an effect on the embryonic development by regulating maternal-fetal thyroid hormone metabolism.