Clinical study of the relationship between cellular adhesion molecules and left ventricular geometry and function in patients with obstructive sleep apnea syndrome and prehypertension / 中华超声影像学杂志

Objective:To investigate the correlations between serum E selectin, intercellular adhesion molecule 1 (ICAM-1), vascular cell adhesion molecule 1 (VCAM-1) and left ventricular geometry and function in patients with obstructive sleep apnea syndrome (OSAS) combined with prehypertension (pre-HT).Methods:A total of 462 patients with pre-HT and OSAS diagnosed by polysomnography (PSG) in the sleep monitoring unit of the Department of Respiratory and Critical Care Medicine at the First Hospital of Shanxi Medical University from July 2019 to July 2022 were restrospectively analysed, and 52 patients with pure pre-HT (pre-HT group) and 73 patients with pure OSAS (OSAS group) in the same period were selected as the control group. OSAS and pre-HT patients were divided into four groups according to left ventricular geometry: normal geometry (NG) group, concentric remodeling (CR) group, eccentric hypertrophy (EH) group and concentric hypertrophy (CH) group. The general clinical data, PSG parameters, blood biochemical parameters and left ventricular structure and function parameters were compared among the six groups. Pearson correlation and multivariate Logistic regression were used to analyze the correlation between E-selection, ICAM-1, VCAM-1, general clinical data, PSG parameters, blood biochemical parameters with left ventricular geometry and function.Results:①Serum E selectin, ICAM-1, and VCAM-1 concentrations increased sequentially from the NG, CR, and EH to CH groups, with the most significant increase in CH group (all P<0.05). In addition, there were statistically significant differences in age, body mass index (BMI), OSAS severity, neck circumference, waist circumference, systolic blood pressure (SBP), diastolic blood pressure (DBP), Glu, lowest oxygen saturation (Lowest-SaO 2), mean oxygen saturation (Mean-SaO 2), percentage of time with oxygen saturation below 90% of total sleep time (T90), left ventricular end-diastolic diameter (LVEDd), interventricular septal thickness (IVST), left ventricular posterior wall thickness (LVPWT), left ventricular mass index (LVMI), relative ventricular wall thickness (RWT), left ventricular ejection fraction (LVEF), peak mitral early diastolic flow velocity/peak mitral late diastolic flow velocity (E/A), E wave deceleration time (DT), A wave duration (AD), and isovolumic relaxation time (IVRT), and overall long-axis longitudinal strain (GLS) and so on(all P<0.05). ②Pearson correlation analysis showed that E selectin was negatively correlated with LVEF, E/A, e′, E/e′, IVRT, and GLS ( r=-0.236, -0.131, -0.224, -0.215, -0.285, -0.336; all P<0.05). ICAM-1 was negatively correlated with LVEF, E, E/A, e′, IVRT, and GLS( r=-0.130, -0.129, -0.104, -0.351, -0.252, -0.259; all P<0.05). VCAM-1 was negatively correlated with E, e′, and IVRT ( r=-0.132, -0.312, -0.387; all P<0.001). ③Multifactorial logistic regression analysis showed that E selectin and VCAM-1 were independently correlated with EH (β=1.139, OR=3.124, P=0.030; β=1.288, OR=3.626, P<0.001) and with CH (β=1.178, OR=3.248, P=0.013; β=1.108, OR=3.028, P<0.001). Conclusions:E selection and VCAM-1 were independently correlated with hypertrophic left ventricular geometry, suggesting that E selectin and VCAM-1 may be involved in the process of abnormal left ventricular structure and function in patients with OSAS combined with pre-HT.

Analysis of intercellular communication patterns in facioscapulohumeral muscular dystrophy based on single-cell nuclear transcriptome sequencing / 国际生物医学工程杂志

Objective:To analyze the patterns of intercellular communication in facioscapulohumeral muscular dystrophy (FSHD) by single-cell nuclear transcriptome sequencing.Methods:Bilateral asymmetrical lesions mouth orbicular muscle of two patients with FSHD and mouth orbicular muscle of two healthy patients were selected. Six samples were obtained, and were divided into control group, mild group and severe group. The normal orbicularis muscle sample was collected from 2 healthy individuals (the control group). The muscle samples in the mild group were from two patients with relatively normal muscle sides, and the samples in the severe group were from two patients with more severe muscle damage sides. Single-cell nuclear transcriptome sequencing was performed on all cells of the three groups. Reduced dimension clustering and cell definition were performed to identify differentially expressed genes and enrichment pathways. Intercellular communication patterns among major cell types and key signaling pathways were explored by cellular communication analysis.Results:Differential gene expression analysis of FSHD bilateral muscle samples identified 46 functionally differentially expressed genes associated with the disease in different cell types, related to apoptosis, oxidative stress, immune inflammation, and muscle function. Intercellular communication was generally increased in the severe group. Fibro-adipogenic progenitors (FAPs) and macrophages are important signaling sources in the abnormal muscle microenvironment of FSHD and are closely associated with disease progression. There are six unique signaling pathways in the mild group, including bone morphogenetic proteins (BMP), transforming growth factor-β (TGF-β), CXC motif chemokine ligand (CXCL), adhesion G protein-coupled receptor E5 (ADGRE5), interleukin-16 (IL-16), and wingless-type MMTV integration site family (WNT) signaling pathways. These signaling pathways are mainly involved in the interaction between macrophages, FAPs, and adipocytes and may be involved in the regulation of fat deposition and fibrosis changes in the diseased muscle.Conclusions:Single-cell nuclear transcriptome sequencing provides a relatively comprehensive pattern of intercellular communication between key cell types in FSHD, providing an appropriate reference for understanding the intercellular regulatory mechanisms of the FSHD muscle microenvironment.

The expression of adhesion molecules in Z310 cells induced by combined exposure to black carbon and lead / 中国职业医学

Objective: To investigate the effects of combined exposure to black carbon and lead on the expression of cell adhesion molecules and their regulating microRNAs (miRNAs) in the rat choroid plexus epithelial Z310 cells. Methods: i) Z310 cells were randomly divided into control group, black carbon exposure group, lead exposure group and combined exposure group. The lead exposure group and black carbon exposure group were treated with 10 μmol/L lead acetate and 10 mg/L black carbon, respectively, and the combined exposure group was treated with both in the above doses. After 12.0 hours, the expressions of intercellular adhesion molecule-1 (ICAM-1), vascular cell adhesion molecule-1 (VCAM-1), and mucosal vascular addressin cell adhesion molecule-1 (MAdCAM-1) in Z310 cells was detected by Western blotting. The expression of miR-326, miR-328-3p and miR-542-3p which regulated ICAM-1 was detected by real-time fluorescent quantitative polymerase chain reaction. ii) Z310 cells or Z310 cells transfected with miRNA-326 mimic were randomly divided into control group, miRNA-326 transfection control group, combined exposure group and miRNA-326 transfection combined exposure group. Cells in the two control groups were not treated. The two combined exposure groups were treated with 10 mg/L black carbon and 10 μmol/L lead acetate for 12.0 hours. The expression of ICAM-1 was detected by Western blotting. Results: i) The relative expression of ICAM-1, VCAM-1 and MAdCAM-1 in the cells of black carbon exposure group and ICAM-1 in the lead exposure group was higher than those in the control group (all P<0.05). The relative expression of ICAM-1 and MAdCAM-1 in the combined exposure group was higher than those in the other three groups (all P<0.05). The relative expression of VCAM-1 in cells of combined exposure group was higher than those in the control group and lead exposed group (all P<0.05). The relative expression of miR-326 in cells of the lead exposure group and black carbon exposure group was lower than those in the control group (all P<0.05). The relative expression of miR-326 in the combined exposure group was lower than that in the other three groups (all P<0.05). There was no significant difference between miR-328-3p and miR-542-3p in the four groups (all P>0.05). ii) The relative expression of ICAM-1 in cells of the miR-326 transfection control group cells was lower than that in the control group (P<0.05), while in the cells in the combined exposure and miRNA-326 transfection combined exposure group, it was higher than that in the control and miRNA-326 transfection control groups (all P<0.05), and lower in the miRNA-326 transfection combined exposure group than in the combined exposure group (P<0.05). Conclusion: Black carbon or lead exposure can upregulate the expression of ICAM-1, VCAM-1 and MAdCAM-1 in Z310 cells. Black carbon and lead combined exposure lead to a synergistic effect on upregulation of ICAM-1 and MAdCAM-1 expression, particularly ICAM-1. The combined exposure of black carbon and lead may upregulate the expression of ICAM-1 by downregulating the expression of miR-326.

Single-cell profiling reveals Müller glia coordinate retinal intercellular communication during light/dark adaptation via thyroid hormone signaling

Light adaptation enables the vertebrate visual system to operate over a wide range of ambient illumination. Regulation of phototransduction in photoreceptors is considered a major mechanism underlying light adaptation. However, various types of neurons and glial cells exist in the retina, and whether and how all retinal cells interact to adapt to light/dark conditions at the cellular and molecular levels requires systematic investigation. Therefore, we utilized single-cell RNA sequencing to dissect retinal cell-type-specific transcriptomes during light/dark adaptation in mice. The results demonstrated that, in addition to photoreceptors, other retinal cell types also showed dynamic molecular changes and specifically enriched signaling pathways under light/dark adaptation. Importantly, Müller glial cells (MGs) were identified as hub cells for intercellular interactions, displaying complex cell‒cell communication with other retinal cells. Furthermore, light increased the transcription of the deiodinase Dio2 in MGs, which converted thyroxine (T4) to active triiodothyronine (T3). Subsequently, light increased T3 levels and regulated mitochondrial respiration in retinal cells in response to light conditions. As cones specifically express the thyroid hormone receptor Thrb, they responded to the increase in T3 by adjusting light responsiveness. Loss of the expression of Dio2 specifically in MGs decreased the light responsive ability of cones. These results suggest that retinal cells display global transcriptional changes under light/dark adaptation and that MGs coordinate intercellular communication during light/dark adaptation via thyroid hormone signaling.

Research advances on extracellular vesicles-based regulation by traditional Chinese medicines and the relationship with TCM "Qi" / 药学学报

Extracellular vesicles (EVs) are an important type of active microvesicles. EVs encapsulate and transfer functional substances such as miRNAs, transcription factors and proteins, which are important vectors for cell communication and organ dialogue. In recent years, studies have shown that quite a number of Chinese medicinal herbs have the pharmacological effect of regulating EVs, and play a unique trans-organ and remote role in the treatment of diseases. Some Chinese medicinal herbs also contain plant-derived EVs themselves, which can be directly involved in the treatment of diseases. As one of the core theories of raditional Chinese medicines (TCM), Qi plays a variety of important roles in the physiological and pathological processes of human body and pharmacology. However, the scientific connotation of Qi′s role and the potential material carrier are still unclear. The latest research suggests that the effect of EVs is potentially related to that of Qi. Therefore, this paper reviews the effect of Qi nourishing Chinese medicinal herbs in regulating EVs in the treatment of cardiovascular diseases, nervous system diseases, liver diseases, renal diseases, malignant tumors and other diseases in recent years. EVs may play an important role in the pharmacological effect of some Chinese medicinal herbs in the treatment of diseases as an intermediary substance. EVs have the characteristics of long-distance transportation, which is consistent with the movement of Qi in TCM. EVs carry a variety of functional molecules, which is consistent with the function of Qi. As the potential material basis of Qi in TCM, the function of EVs is worth further study.

Design and applications of synthetic electroactive microbial consortia / 生物工程学报

Synthetic electroactive microbial consortia, which include exoelectrogenic and electrotrophic communities, catalyze the exchange of chemical and electrical energy in cascade metabolic reactions among different microbial strains. In comparison to a single strain, a community-based organisation that assigns tasks to multiple strains enables a broader feedstock spectrum, faster bi-directional electron transfer, and greater robustness. Therefore, the electroactive microbial consortia held great promise for a variety of applications such as bioelectricity and biohydrogen production, wastewater treatment, bioremediation, carbon and nitrogen fixation, and synthesis of biofuels, inorganic nanomaterials, and polymers. This review firstly summarized the mechanisms of biotic-abiotic interfacial electron transfer as well as biotic-biotic interspecific electron transfer in synthetic electroactive microbial consortia. This was followed by introducing the network of substance and energy metabolism in a synthetic electroactive microbial consortia designed by using the "division-of-labor" principle. Then, the strategies for engineering synthetic electroactive microbial consortiums were explored, which included intercellular communications optimization and ecological niche optimization. We further discussed the specific applications of synthetic electroactive microbial consortia. For instance, the synthetic exoelectrogenic communities were applied to biomass generation power technology, biophotovoltaics for the generation of renewable energy and the fixation of CO2. Moreover, the synthetic electrotrophic communities were applied to light-driven N2 fixation. Finally, this review prospected future research of the synthetic electroactive microbial consortia.

Effects of nano lead oxide exposure on cognitive function and inflammatory mechanism of leukocyte infiltration in mice / 中华行为医学与脑科学杂志

Objective:To investigate the effect of nano lead oxide (nano-PbO) exposure on learning and memory as well as spatial exploration ability in the mice, and the role of leukocyte infiltration of brain tissue in neurobehavioral damage caused by nano-PbO exposure.Methods:A total of 60 male SPF grade Kunming mice were divided into control group, low-dose nano-PbO group, medium-dose nano-PbO group and high-dose nano-PbO group according to body mass matching method, with 15 mice in each group.Mice in low, medium and high dose groups of nano-PbO were intraperitoneally injected with 5 mg·kg -1, 10 mg·kg -1, 20 mg·kg -1 nano-PbO, respectively. And mice in the control group were intraperitoneally injected with the same volume of 0.9% normal saline.The frequency of intervention was once a day for 28 days.Morris water maze test and open field test were used to detect the ability of learning and memory and spatial exploration of mice. Western blot was used to detect the protein expression of tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β) in hippocampus of mice, intercellular cell adhesion molecule-1 (ICAM-1), vascular cell adhesion molecule-1 (VCAM-1) in mouse microvessels and lymphocyte function-associated antigen-1 (LAF-1) in mouse blood leukocyte. The proportion of leukocytes in mouse brain was detected by flow cytometry. All statistical analyses were performed by SPSS 20.0. Morris water maze data were analyzed by repeated measures ANOVA, the other data among multiple groups were compared by one-way ANOVA, and Tukey's test was used for further pairwise comparison.Pearson correlation analysis was performed to evaluate the correlation between neurobehavioral indexes and the proportion of white blood cells, TNF-α and IL-1β in brain tissue. Results:Morris water maze results showed that the escape latency of the four groups of mice had a significant interaction between group and time( F=3.21, P<0.05). The escape latencies of mice in middle and high dose groups of nano-PbO were higher than that in the control group (both P<0.05), and the numbers of crossing the platform of the two groups were lower than that in the control group (both P<0.05). The results of open field test showed that there was a statistically significant difference in the residence time of the mice in the four groups ( F=119.10, P<0.01). The total standing times of mice in the middle group and high dose group of nano-PbO were lower than that in the control group (both P<0.01). The results of Western blot showed that the levels of TNF-α and IL-1β in hippocampus tissue of mice were significant differences among the four groups ( F=7.21, 9.89, both P<0.05). The levels of TNF-α and IL-1β in the hippocampus of mice in the high-dose nano-PbO group were higher than those in the control group (TNF-α: (0.35±0.10), (1.03±0.30), P<0.05; IL-1β: (0.32±0.10), (0.50±0.15), P<0.05). The results of flow cytometry analysis showed that the proportions of leukocytes in the brain tissue of mice in the low, medium and high dose groups of nano-PbO were (9.99±1.09)%, (13.03±0.94)% and (16.51±3.89)%, respectively. Among them, the proportions of leukocytes in the middle and high dose groups of nano-PbO were significantly higher than that in the control group((8.13±1.29)%) (both P<0.05). The results of correlation analysis showed that the proportion of leukocytes, levels of TNF-α, IL-1β protein of hippocampus in the medium, high dose groups of nano-PbO were negatively correlated with the behavioral indexes ( r=-0.815, -0.744, -0.578, all P<0.01; r=-0.771, -0.836, -0.704, all P<0.05; r=-0.823, -0.876, -0.695, all P<0.05). The results of Western blot showed that the levels of ICAM-1 and VCAM-1 in cerebral microvessels of mice in the four groups were significantly different ( F=5.51, 16.19, both P<0.05). The levels of ICAM-1 and VCAM-1 in the middle and high dose groups of nano-PbO were higher than those in the control group(ICAM-1: (1.07±0.16), (1.21±0.35), (0.59±0.19), all P<0.05; VCAM-1: (0.68±0.12), (1.92±0.23), (0.23±0.05), both P<0.05). In addition, there was a significant difference in the level of LFA-1 protein in blood leukocytes of mice in the four groups ( F=41.80, P<0.05). The levels of LFA-1 in the middle and high dose groups of nano-PbO were higher than that in the control group((0.33±0.06), (0.89±0.23), (0.05±0.01), both P<0.05). Conclusion:The nano-PbO exposure can lead to cognitive impairment and increased inflammatory factors in the hippocampus of mice, which may be related to the increase of ICAM-1 and VCAM-1 in vascular endothelial cells, which promotes leukocyte infiltration into brain tissue.

New insights into the integrity of intercellular junctions between retinal pigment epithelial cells / 中华实验眼科杂志

Retinal pigment epithelium (RPE) is composed of a layer of highly specialized hexagonal pigment epithelial cells.The apical surface of RPE interacts with the photoreceptor, and RPE basal surface interacts with Bruch membrane and choroidal capillaries to maintain the function of retinal photoreceptor.A variety of junction proteins distributed between RPE cells are the basis for RPE to perform normal functions, ensuring the integrity and physiological function of RPE.Under pathological conditions, the abnormal function of RPE is first manifested by the abnormal junctional protein, which leads to the loss of adhesion between cells, cells and basement membrane, and then a series of abnormal biological behaviors, such as dissociation, migration, transdifferentiation and protein expression changes in RPE cells, which have become an important cause of many fundus diseases.The role of RPE junctional complexes during normal and pathological conditions, as well as their role in proliferative vitreoretinopathy, age-related macular degeneration and diabetic vitreoretinopathy was reviewed in this article from the composition and correlation of junctional proteins between RPE cells.

Epithelial Cell Adhesion Molecules (EpCAMs) Promote Drug Resistance in Breast Cancer Cells by Enhancing Tight Junctions / 中国生物化学与分子生物学报

Breast cancer is a malignant tumor with high mortality, and multidrug resistance (MDR) mediated by ABCG2 (ATP-Binding cassette G2) is an important cause of chemotherapy failure. It is an urgent problem to explore the mechanism of ABCG2-mediated drug resistance and its key molecules. Epithelial cell adhesion molecule (EpCAM) is involved in multiple tumor drug resistance and is closely related to breast cancer MDR. However, its role in ABCG2-mediated breast cancer drug resistance has not been clarified. The purpose of this study was to explore the regulation of EpCAM on ABCG2-mediated MDR in breast cancer cells and its mechanism. CCK8 cytotoxicity assays confirmed that the drug resistance of MCF-7/MX cell line to mitoxantrone (MX) was significantly increased compared with MCF-7 drug-sensitive strain of human breast cancer. Western blotting results showed that ABCG2 was highly expressed and EpCAM was up-regulated in MCF-7/MX cells compared with MCF-7. SiRNA knockdown of EpCAM in MCF-7/MX cells down-regulated ABCG2 expression and restored sensitivity to MX. Cell morphology was observed under an inverted microscope, and it was found that knocking down EpCAM reduced cell-cell connections between MCF-7/MX cells. The co-localization of EpCAM and claudin 1 in MCF-7/MX cells was observed by immunofluorescence. Furthermore, Western blotting results showed that EpCAM knockdown reduced claudin 1 expression in MCF-7/MX cells. In conclusion, EpCAM may promote ABCG2-mediated mMDR in breast cancers by enhancing intercellular tight junctions through interaction with claudin 1.

Effect of Tanxiang Qingyan Tablets on MyD88/NF-κB/ICAM-1 signaling pathway in rats with chronic bronchitis / 中国药理学通报

Aim To explore the effect of Tanxiang Qingyan Tablets on rat model with chronic bronchitisand the effect of MyD88/NF-κB/ICAM-1 signaling pathway expression in bronchopulmonary tissues of rats.Methods A rat model of chronic bronchitis was established by smoking method combined with lipopolysaccharide(LPS,2g·L-1)tracheal injection.The rats were randomly divided into normal group,sham operation group,model group,and positive drug(Guilong Ruikening tablets)1 g·kg-1)group,Tanxiang Qingyan Tablet high,medium and low dose(1.44,0.72,0.36 g·kg-1)group,with intragastric interventionin continuous 15 days.The pathological changes of bronchopulmonary tissues were observed by HE staining,and the infiltration of bronchial inflammatory cells was counted; ELISA method was used to detect the contents of tumor necrosis factor(TNF-α)and interleukin 10(IL-10)in peripheral serum; Western blot and immunohistochemical methodswere employed to detectmyeloid cell differentiation protein 88(MyD88),nuclear transcription factor-κB(NF-κB)and anti-intercellular adhesion molecule 1(ICAM-1)protein expression in bronchopulmonary tissues.Results Compared with normal group and sham operation group,the bronchial mucosal epithelial cells of model group were severely damaged,the alveolar septum was widened,the bronchial inflammatory infiltrationsignificantly increased,the serum TNF-α levels significantly increased,IL-10 levels decreased, and MyD88,NF-κB and ICAM-1 protein expression levels increased significantly(P<0.05,0.01)in bronchopulmonary tissues; compared with model group,the pathological damage and inflammatory changes of the bronchopulmonary tissues of rats in Tanxiang Qingyan Tablet group were reduced,and the serum TNF-α content was significantly reduced,IL-10 content did not change significantly,and MyD88,NF-κB and ICAM-1 protein expression levels in bronchopulmonary tissues were significantly down-regulated(P<0.05,0.01).Conclusions Tanxiang Qingyan Tablets can effectively improve bronchopulmonary tissue inflammatory infiltration,which may be related to reducing the release of inflammatory mediators such as TNF-α and regulating the expression of MyD88/NF-κB/ICAM-1 signaling pathway.

Therapeutic effects of the extract of Sancao Formula, a Chinese herbal compound, on imiquimod-induced psoriasis via cysteine-rich protein 61 / 中西医结合学报

OBJECTIVE@#Psoriasis is a common chronic inflammatory skin disease that is prone to recurrence, and the proinflammatory factor, cysteine-rich protein 61 (Cyr61), is important in its pathophysiology. Long-term clinical practice has shown that Sancao Formula (SC), a Chinese herbal compound, is effective in the treatment of psoriasis, but the precise mechanism remains unknown. In this study, we investigate the mechanism by which SC extract alleviates imiquimod (IMQ)-induced psoriasis.@*METHODS@#The expression of Cyr61 in psoriatic lesions and normal healthy skin was detected using immunohistochemical analysis to investigate the biological role of Cyr61 in models of psoriatic inflammation. A psoriatic mouse model was established by topical application of IMQ, and the effect of topical application of SC extract was evaluated using the psoriasis area and severity index (PASI) score, hematoxylin-eosin staining, and histopathological features of the skin. Next, a HaCaT cell inflammation model was established using interferon-γ (IFN-γ), and the effect of SC extract on the mRNA and protein levels of Cyr61 and intercellular cell adhesion molecule-1 (ICAM-1) was confirmed using Western blot and quantitative real-time polymerase chain reaction analyses.@*RESULTS@#Immunohistochemical staining showed that the expression of Cyr61 in psoriatic lesions was higher than that in normal skin samples (78.26% vs 41.18%, P < 0.05), and the number of Cyr61-positive cells in psoriatic lesions was also significantly higher than in normal skin (18.66 ± 2.51 vs 4.33 ± 1.52, P < 0.05). Treatment in mice with IMQ-induced psoriasis showed that SC extract could significantly improve the inflammatory phenotype, PASI score (10.875 ± 0.744 vs 3.875 ± 0.582, P < 0.05), and pathological features compared with those in IMQ model group; SC treatment was also associated with decreased levels of Cyr61 and ICAM-1. In the IFN-γ-induced inflammatory cell model, the mRNA and protein levels of Cyr61 and ICAM-1 were upregulated, while the SC extract downregulated the levels of Cyr61 and ICAM-1.@*CONCLUSION@#The results provide a theoretical basis for the involvement of Cyr61 in the pathogenesis of psoriasis, and suggest that SC should be used to target Cyr61 for the prevention of psoriasis recurrence.

Targeting TSHR and ICAM-1 for treatment of Graves′ disease in BALB/c mice / 中华核医学与分子影像杂志

Objective:To explore new methods of treating Graves′ disease (GD) by targeting thyroid stimulating hormone receptor (TSHR) and intercellular adhesion molecule-1 (ICAM-1).Methods:The small interfering RNA (siRNA) targeting TSHR and the ICAM-1 monoclonal antibody (mAb) were designed and synthesized. Thirty GD model mice were randomly divided into siRNA treatment group, ICAM-1 mAb treatment group, and untreated GD group (10 mice in each group), and 10 normal mice were taken as blank control. Serum thyroxine (T 4), thyroid stimulating hormone (TSH), TSH receptor-stimulating antibody (TSAb) and TSH-stimulation blocking antibody (TSBAb) were measured before and after treatment. At the end of the treatment, body mass and heart rate of mice in each group were measured, and thyroid uptake of 99Tc mO 4-, thyroid size and pathological changes were evaluated. Independent-sample t test, paired t test and one-way analysis of variance were used to analyze data. Results:After three treatments, the body mass of mice in siRNA group and ICAM-1 mAb group were significantly lower than that of normal mice ( F=3.50, P=0.025); the heart rates of the mice in two groups were significantly lower than that of untreated GD mice ( F=24.73, P<0.001). Heart rate of mice treated with siRNA decreased significantly, close to that of normal mice. After treatment, the serum T 4((27.58±1.94) vs (65.71±6.89) μg/L, (27.24±3.50) vs (70.84±8.46) μg/L), TSAb ((331.44±43.38) vs (457.33±45.85) mU/L, (275.16±45.80) vs (443.91±42.32) mU/L) and TSBAb ((13.94±1.11) vs (15.83±5.92) mU/L, (14.59±1.02) vs (17.05±6.16) mU/L) levels of mice in both siRNA group and ICAM-1 mAb group significantly decreased ( t values: 4.45-10.87, all P<0.05), while the serum TSH levels of mice in two groups significantly increased ((0.13±0.05) vs (0.04±0.05) mU/L, (1.46±0.34) vs (0.06±0.03) mU/L; t values: -2.22, -5.87, P values: 0.007, <0.001). The elevated TSH level and decreased TSAb level of mice treated with ICAM-1 mAb were significantly different from those treated with siRNA ( t values: 1.03, -1.63, P values: 0.002, 0.031). After treatment, the uptake of 99Tc mO 4- in part of the thyroid lobes of mice was decreased, and the enlargement degree of the corresponding lobes was reduced. The thyroid pathology of mice in the treated groups showed that the absorption vacuoles of thyroid follicles were reduced, and the phenomenon of thinner colloids was improved. No obvious damage was observed in the heart, liver and kidneys of the mice. Conclusions:Both the siRNA targeting TSHR and ICAM-1 mAb have therapeutic effects on GD model mice. The siRNA is better at controlling heart rate, and ICAM-1 mAb is better at increasing TSH and decreasing TSAb. Each of the above treatment methods is safe and effective, which can provide new ideas for GD targeted therapy.

Excessive iodine promotes the occurrence and development of experimental autoimmune thyroiditis in mice through p38 and intercellular adhesion molecule-1 / 中华地方病学杂志

Objective:To investigate the molecular mechanism of excessive iodine induced experimental autoimmune thyroiditis (EAT) in mice.Methods:Sixty female non-obese diabetic (NOD) mice were selected and divided into 5 groups according to body weight [(25 ± 3) g] via the random number table method, with 12 mice in each group: control group (group A), 10-fold high iodine group (group B), 100-fold high iodine group (group C), 1 000-fold high iodine group (group D) and 1 000-fold high iodine combined with polyinosinic acid-polycytidylic acid [Poly (I:C)] group (group E). The experiment period was 16 weeks. Mice in each group drank purified water with sodium iodine (NaI) content of 0.000, 0.005, 0.050, 0.500 and 0.500 mg/L, respectively; mice in group E were intraperitoneally injected with Poly (I:C) at week 7 and week 15, respectively. At the end of the 16th week, mice were dissected and blood samples and thyroid tissue were taken. The levels of serum thyroid function indexes [thyroid stimulating hormone (TSH), free triiodothyronine (FT 3), free thyroxine (FT 4), and thyroid peroxidase antibody (TPOAb)] were detected by enzyme-linked immunosorbent assay (ELISA); the pathological changes of thyroid tissue were observed after hematoxylin-eosin (HE) staining; differentially expressed genes in thyroid tissue were detected by RNA-sequencing (RNA-seq), and analyzed by KEGG pathway; mRNA and protein levels of p38, intercellular adhesion molecule-1 (ICAM-1) and chemokine 10 (CXCL10) in thyroid tissue were detected by real-time fluorescence quantitative PCR (qPCR) and Western blotting, respectively. Results:There were statistically significant differences in serum levels of TSH (ng/ml: 6.53 ± 0.86, 6.61 ± 0.82, 7.68 ± 0.55, 7.93 ± 0.60, 8.73 ± 1.60), FT 3 (pg/ml: 59.35 ± 10.16, 53.73 ± 10.96, 46.19 ± 8.03, 41.01 ± 8.67, 34.21 ± 11.75), FT 4 (pg/ml: 136.74 ± 10.06, 124.33 ± 14.34, 101.80 ± 6.78, 91.37 ± 6.75, 73.29 ± 17.31), and TPOAb (U/ml: 130.81 ± 24.53, 145.47 ± 28.89, 166.52 ± 41.59, 199.78 ± 42.19, 201.99 ± 44.03) among the 5 groups of mice ( F = 4.77, 4.96, 23.12, 3.68, P < 0.05). Compared with group A, the serum TSH levels of mice in groups C, D and E were higher, the levels of FT 3 and FT 4 in groups B, C, D and E were lower, and the levels of TPOAb in groups D and E were higher, and the differences were statistically significant ( P < 0.05). HE staining showed that the thyroid follicle lesion in groups D and E was serious, and the EAT phenotype appeared in both groups. The differentially expressed genes were analyzed by KEGG pathway. Compared with group A, 8 metabolic pathways related to thyroid autoimmunity and inflammation were found in groups B, C, D and E. Further analysis found that 3 genes appeared in multiple pathways, namely p38, ICAM-1 and CXCL10. There were significant differences in the mRNA levels of p38, ICAM-1 and CXCL10 in thyroid tissue of the 5 groups of mice ( F = 14.77, 12.76, 16.39, P < 0.05); compared with group A, the mRNA levels of p38 in groups B, C, D and E were higher, and the mRNA levels of ICAM-1 and CXCL10 in groups C, D and E were higher ( P < 0.05). There were significant differences in the protein levels of p38, ICAM-1 and CXCL10 in thyroid tissue of the 5 groups of mice ( F = 7.97, 73.86, 18.02, P < 0.05); compared with group A, the protein levels of ICAM-1 and CXCL10 in groups B, C, D and E were higher ( P < 0.05). Conclusion:Excessive iodine promotes the occurrence and development of EAT in mice by up-regulating the expressions of p38 and ICAM-1 genes that are closely related to thyroid autoimmune and inflammatory responses.

Cornuside ameliorated experimental autoimmune encephalomyelitis by limiting the recruitment of CD4+ T lymphocytes in the spinal cord

We conducted this study to determine whether cornuside could improve the neurological deficit symptoms of experimental autoimmune encephalomyelitis (EAE) rats, as well as determine the potential involvement of CD4+ T lymphocytes, vascular cell adhesion molecule-1 (VCAM-1), intercellular adhesion molecule-1 (ICAM-1), and tumor necrosis factor-α (TNF-α). Altogether, 32 Lewis rats were randomly divided into control, EAE, EAE/prednisolone, and EAE/cornuside, wherein their neurological function was assessed every day. CD4+ T lymphocyte recruitment into the spinal cord (SC) was evaluated using immunohistochemistry. The VCAM-1, ICAM-1 and TNF-α mRNA expressions in the SC were determined by real-time quantitative PCR, and the VCAM-1 and ICAM-1 proteins were determined by western blotting. Compared to the control group, the EAE group rats with neurological deficits had enhanced CD4+ T lymphocyte infiltration and higher expression levels of VCAM-1, ICAM-1, and TNF-α in the SC. Meanwhile, compared with the EAE group, the EAE/cornuside and EAE/prednisolone groups had lower neurological scores, less CD4+ T lymphocyte infiltrations, and lower expression levels of VCAM-1, ICAM-1, and TNF-α in the SC. Thus, cornuside ameliorated EAE, which could be owed to the inhibition of CD4+ T lymphocyte recruitment and VCAM-1, ICAM-1, and TNF-α expressions in the SC

Utilidad del suero autólogo en lesiones de superficie ocular de evolución incierta. Evaluación clínica e imagenológica

Objetivo: Determinar la efectividad del suero autólogo rico en factores de crecimiento en la reparación de lesiones de la superficie ocular de evolución incierta con el tratamiento convencional. Materiales y métodos: Se trataron 46 unidades oculares con afecciones de la superficie ocular agrupadas en queratopatías por exposición, queratopatías por síndrome de ojo seco / neurotróficas, y traumas oculares. Las partes oculares afectadas fueron: conjuntiva, cornea (epitelio, estroma) y esclera. Se evaluaron de manera anatómica y funcional con la prueba de Schirmer, tinción con Fluoresceína y tomografía de coherencia óptica (TCO) entre marzo y diciembre del 2020. Resultados: Los síntomas mejoraron en el siguiente orden: dolor ocular, sensación de cuerpo extraño, blefaroespasmo, hiperemia y lagrimeo. Las lesiones evolucionaron favorablemente de la siguiente manera: en primer lugar las conjuntivales y del epitelio corneal, luego las del estroma corneal y finalmente las lesiones en la esclera. Se obtuvo una media de 15 días para recuperación inmediata de la superficie y de 21 días para recuperación tardía. Las lesiones con adelgazamiento parcial profundo de esclera tomaron alrededor de 2 meses. Conclusiones: Los hallazgos relacionados al umbral del dolor, tiempo de recuperación, remodelación cicatrizal del tejido afectado y recuperación de la agudeza visual son prometedores e importantes. La utilización de suero autólogo rico en factores de crecimiento puede ser una alternativa terapéutica para las lesiones de difícil resolución con el tratamiento convencional.

Objective: To determine the effectiveness of autologous serum rich in growth factors to repair ocular surface lesions which have uncertain progression with conventional treatment. Materials and methods: AForty-six (46) eyes with ocular surface disorders such as exposure keratopathy, keratopathy caused by dry eye syndrome, neurotrophic keratopathy and blunt eye injury were treated. The affected areas were the conjunctiva, cornea (epithelium, stroma) and sclera. Anatomical and functional evaluations were performed between March and December 2020 using Schirmer's test, fluorescein eye stain and optical coherence tomography (OCT). Results: The symptoms improved in the following order: eye pain, foreign body sensation, blepharospasm, hyperemia and epiphora. Additionally, the lesions progressed favorably as follows: first, those of the conjunctiva and corneal epithelium; then, those of the corneal stroma; and, finally, those of the sclera. An average of 15 days was required for immediate ocular surface recovery and 21 days for late recovery. The lesions with total scleral thinning healed in about two months. Conclusions: The findings related to pain threshold, recovery time, scar tissue remodeling of the affected tissue and visual acuity improvement are promising and important. Using autologous serum rich in growth factors may be a therapeutic alternative for those lesions that are difficult to resolve with conventional treatment.

Melatonin inhibiting the migration and invasion of gastric cancer cell line SGC-7901 / 解剖学报

Objective To investigate the inhibitory effect of melatonin on the migration and invasion of gastric cancer cell and the underlying molecular mechanism. Methods Human gastric cancer SGC-7901 cells were treated with different concentrations of melatonin ( 0. 1, 1, 2 and 4 mmol/L ) for 24 hours, and the changes in the migration and invasion of gastric cancer cells were detected by scratch test and Transwell assay. The expressions of matrix metalloproteinase ( MMP) -2 and MMP-9 in the supernatant were detected by ELISA kit. The changes of MMP-2, MMP-9, intercellular cell adhesion molecule-1 ( ICAM-1 ) and CD44 expressions were detected by using Real-time PCR. The protein expressions of ICAM-1, CD44, p-P38, P38 and phosphorylated mitogen-activated protein kinase kinase ( p-MKK) 3/6 were detected by Western blotting. Results Melatonin inhibited the migration and invasion of gastric cancer cells in a dose- dependent manner. Compared with the blank control group, melatonin reduced the expression of MMP-2, MMP-9, ICAM-1 and CD44, and inhibited the expressions of p-P38, P38 and p-MKK3/6 in gastric cancer cells. Conclusion Melatonin inhibits the migration and invasion of gastric cancer cells by inhibiting the expressions of MMP-2, MMP-9, ICAM-1 and CD44. Inhibition may be related to the p38MAPK signaling pathway.

Advances on the mechanisms regulating the formation of the biofilm of Listeria monocytogenes / 生物工程学报

Listeria monocytogenes is an important food-borne pathogen. The distribution and survival of L. monocytogenes are related to its ability to form biofilms. Biofilms are resistant to adverse environments, and bacteria separated from the biofilms may lead to persistent food contaminations. The formation, maturation and structure of biofilms depend on a variety of external and internal factors, among which a variety of regulatory mechanisms play important roles. This review summarizes the regulatory mechanisms (including intracellular, intercellular and interspecific interactions) involved in the biofilm formation of L. monocytogenes in order to control the biofilm formation in food processing environments, thus providing new intervention strategy for food safety.

Exosomes Derived from Hydroquinone-transformed Human Bronchial Epithelial Cells Inhibited Recipient Cell Apoptosis by transferring miR-221 / 生物医学与环境科学（英文）

Objective@#Although benzene is a confirmed environmental carcinogen, the mechanism of its carcinogenicity remains largely unclear. The suggested oncogene, miR-221, is elevated and plays important roles in various tumors, but its role in benzene-induced carcinogenesis remains unknown.@*Methods@#In the present study, we constructed hydroquinone (HQ, a representative metabolite of benzene with biological activity)-transformed malignant cell line (16HBE-t) and analyzed the level of miR-221 in it with qRT-PCR. Exosomes from 16HBE-t cells incubated with or without an miR-221 inhibitor were isolated by ultracentrifugation, characterized by transmission electron microscopy and laser scanning confocal microscope, and then transfected into 16HBE cells. The effects of exosomal miR-221 on apoptosis induced by HQ in recipient cells were determined using flow cytometry.@*Results@#The amount of miR-221 in 16HBE-t was significantly increased compared with controls. When recipient cells ingested exosomes derived from 16HBE-t, miR-221 was increased, and apoptosis induced by HQ was inhibited. Blocking miR-221 in 16HBE-t using an inhibitor did not significantly alter miR-221 or apoptosis in recipient cells.@*Conclusion@#Exosomal miR-221 secreted by 16HBE-t inhibits apoptosis induced by HQ in normal recipient cells.

Protective effect of sevoflurane preconditioning on lung ischemia-reperfusion injury in rats and its influence on TLR4/MyD88/NF-κB signaling pathway / 器官移植

Objective To evaluate the protective effect of sevoflurane preconditioning on lung ischemia-reperfusion injury (IRI) and its influence on the Toll-like receptor 4 (TLR4)/myeloid differentiation factor 88(MyD88)/nuclear factor (NF)-κB signaling pathway. Methods Forty healthy adult SD rats were randomly divided into the control group (Sham group), lung IRI model group (LIRI group), sevoflurane group (Sev group) and TLR4 inhibitor TAK-242 combined with sevoflurane group (TAK+Sev group), 10 rats in each group. The pathological changes of lung tissues were observed by hematoxylin-eosin (HE) staining and the pathological injury score was graded. The cell apoptosis of lung tissues was detected by terminal deoxynucleotidyl transferase-mediated dUTP nick- end labeling (TUNEL) and the apoptosis rate was calculated. The wet-to-dry (W/D) ratio of lung tissues was measured to determine the water content of lung tissues. The levels of oxidative stress-related parameters in the lung tissues and inflammatory factors in both the lung tissues and serum were detected. The expression levels of TLR4/MyD88/NF-κB signaling pathway-associated proteins in the lung tissues were determined by Western blot. Results Compared with the Sham group, the pathological injury score, W/D ratio, cell apoptosis rate, malondialdehyde (MDA) level, inflammatory factor level and the relative expression levels of TLR4, MyD88 and NF-κB p65 proteins in the lung tissues were significantly increased, whereas the superoxide dismutase (SOD) level and the relative expression level of NF-κB inhibitory protein α(IκBα) were significantly decreased in the LIRI and Sev groups (all P < 0.05). Compared with the LIRI group, the pathological injury score, W/D ratio, cell apoptosis rate, MDA level, inflammatory factor level and the relative expression levels of TLR4, MyD88 and NF-κB p65 proteins were significantly decreased, whereas the SOD level and the relative expression level of IκBα were significantly increased in the Sev and TAK+Sev groups (all P < 0.05). Compared with the Sev group, the pathological injury score, W/D ratio, cell apoptosis rate, MDA level, inflammatory factor level and the relative expression levels of TLR4, MyD88, NF-κB p65 proteins were significantly decreased, while the relative expression level of IκBα was significantly increased in the TAK+Sev group (all P < 0.05). Conclusions Sevoflurane preconditioning may inhibit the activation of TLR4/MyD88/NF-κB signaling pathway and suppress inflammatory reaction and oxidative stress, thereby effectively mitigating the lung IRI.

Research progress on the exosomes in ophthalmic diseases / 国际眼科杂志(Guoji Yanke Zazhi)

@#Exosomes are extracellular vesicles of sizes ranging from 50-150nm in diameter. Exosomes can deliver bioactive molecules(<i>e.g.</i> proteins, lipids, DNA, microRNA, <i>etc.</i>)into target cells which play an important role in cell-cell communication. Researches demonstrated that exosomes mediated cell-cell communication can impact cell apoptosis, invasion, migration, immune response and oxidative repair ability of recipient cells. Recently, researches on exosomes developed rapidly in the field of ophthalmology. This review summarized the latest research progress of exosomes in ophthalmic diseases.