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Aim To investigate the regulatory role and mechanism of resveratrol in inhibiting autophagy and promoting apoptosis in choroidal melanoma cells. Methods Choroidal melanoma cells (MUM2B) were divided into control and experimental groups, and treated with different concentrations of resveratrol (0, 10, 20,40,60,80 μmol ·L
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This study investigated the acute toxicity of fermented Platycodonis Radix on mice and its effect on coughing in mice infected with Mycoplasma pneumoniae. The maximum dosage(MAD) was used in the acute toxicity experiment on mice to observe the signs of mice. After 14 days, dissection, blood biochemical examination, and pathological tissue section observation were conducted. In the pharmacological experiment of fermented Platycodonis Radix, 60 healthy BALB/c mice, 30 males and 30 females, were randomly divided into a blank group, a model group, a carbetapentane group(0.013 g·kg~(-1)·d~(-1)), and high-, medium-, and low-dose fermented Platycodonis Radix groups(5.2, 2.6, and 1.3 g·kg~(-1)·d~(-1)), with 10 mice in each group. Except for the blank group, the mice in the other five groups underwent model induction by intranasally instilling 20 μL of 1×10~6 CCU M. pneumoniae for 3 days, and the mice in each group were orally administered the corresponding drugs for 7 days. Cough induction experiment was conducted to observe and record the cough latency and total cough count within 3 min for each group. Hematoxylin-eosin(HE) staining and Masson staining were used to observe the pathological changes in lung tissues. Immunohistochemistry was performed to observe the protein expression of transient receptor potential A1(TRPA1), calcitonin gene-related peptide(CGRP), and substance P(SP) in the lung tissues of mice in each group. Real-time fluorescence-based quantitative polymerase chain reaction(qRT-PCR) was used to elucidate the changes in the mRNA levels of cough-related factors TRPA1, CGRP, and SP in mice treated with fermented Platycodonis Radix. No mice died in the acute toxicity experiment, and there were no changes in general behavior and major organ histopathological examinations. Compared with the blank group, there were no statistically significant differences in blood biochemical indexes. In the pharmacological experiment of fermented Platycodonis Radix, compared with the model group, the high-and medium-dose fermented Platycodonis Radix groups showed improved lung tissue structure of mice, with clear structure and regular tissue morphology. The qRT-PCR and immunohistochemical detection showed a decrease in the expression of TRPA1, CGRP, and SP in the fermented Platycodonis Radix groups. Fermented Platycodonis Radix can exert an inhibitory effect on cough by suppressing the expression of TRPA1, CGRP, and SP in lung tissues, thereby identifying the target of the drug.
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Animals , Female , Male , Mice , Calcitonin Gene-Related Peptide/analysis , Cough , Drugs, Chinese Herbal/chemistry , Lung , Plant Roots/chemistryABSTRACT
Aim To investigate the role of TGF-β/Smad signaling pathway in rheumatoid arthritis (RA) - associated postinterstitial pulmonary fibrosis in mice. Methods The mouse model of RA was constructed by subcutaneous administration of complete Freund's adjuvant (CFA) and chicken II collagen (Col-II) to the tail root of mice. The blank group was given the same amount of distilled water, and the control group was given the same amount of glacial acetic acid (solvent). The degree of toe swelling (joint swelling degree and arthritis index) was monitored to evaluate the mouse modeling. The pathological changes of mouse lung tissues were observed by HE and Masson staining. The expression of TGF-β in lung tissues were observed by immunohistochemical staining. The level of hydroxyproline in lung tissues was measured by chemiluminescence method. The expressions of Smad2, Smad3 and phosphorylated p-Smad2 and phosphorylated p-Smad3 in lung tissues were detected by Western blot. Results Compared with blank group and solvent group, the joint swelling and arthritis index of model group significantly increased. Twenty-one days after administration, HE staining showed inflammatory changes in lung interstitium of the model group, Masson staining showed collagen fiber deposition and obvious fibrosis in lung interstitium of the model group, and immunohistochemical staining showed that the expression of TGF-β in cytoplasm of lung interstitial cells of the model group increased, which was brown and yellow. Meanwhile, hydroxyproline was significantly raised in lung tissue homogenate of the model group. Further WB analysis showed that compared with blank group and solvent group, the expression of p-Smad2 and pSmad3 in lung tissues of the model group was significantly up-regulated (P < 0. 05, P < 0. 01). Conclusions RA can give rise to pulmonary fibrosis, and the expressions of p-Smad2 and p-Smad3 are up-regulated, which is be pivotal in pulmonary fibrosis and RA-related post-interstitial pulmonary fibrosis.
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Compound reserpine and triamterene tablets (CRTT), a compound antihypertensive drug developed by Chinese scientists, is still widely used in clinical practice. However, the mechanisms by which CRTT treats hypertension remain to be fully understood. This study used network pharmacology to analyze CRTT's antihypertensive mechanisms with in vitro experiments. The targets of the four chemical components of CRTT were collected from the Swiss Target Prediction database; 1 828 protein targets related to hypertension were collected from the Therapeutic Target Database (TTD) and Online Mendelian Inheritance in Man (OMIM) database. The CRTT-hypertension network model was constructed using a search tool for recurring instances of neighbouring genes (STRING). Gene ontology (GO) and pathway enrichment analysis of targets of interest was conducted with the Metascape database. In the in vitro study, human umbilical vein endothelial cells (HUVEC) and vascular smooth muscle cells (VSMC) were treated with 1 μmol·L-1 angiotensin Ⅱ (AngⅡ) and CRTT was administered at concentrations of 0.01, 0.1, and 1 μmol·L-1. Changes in the phosphatidylinositol-3-kinase/protein serine threonine kinase/endothelial nitric oxide synthase (PI3K/Akt/eNOS) pathway in HUVEC and the cyclic guanosine monophosphate/cGMP-dependent protein kinase (cGMP/PKG) pathway in VSMC were determined by Western blot. Network pharmacological analysis revealed that the antihypertensive effect of CRTT is closely associated with biological pathways such as vascular tone regulation, adrenergic receptor activation, protein kinase activity and signaling pathways such as the cGMP/PKG signaling pathway, vascular smooth muscle contraction, neuroactive ligand-receptor interaction, adrenergic signaling in cardiomyocytes and calcium signaling pathways. The in vitro study confirmed that CRTT increased the levels of phosphorylated phosphatidylinositol-3-kinase (p-PI3K), phosphorylated protein serine threonine kinase (p-Akt), phosphorylated endothelial nitric oxide synthase (p-eNOS) in HUVEC and the levels of eNOS, phosphorylated vasodilator-stimulated phosphoprotein (p-VASP), and PKG in VSMC through multiple targets and pathways. These results suggest that the activation of PI3K/Akt/eNOS pathway and endothelial-dependent NO/cGMP signaling may be involved in the CRTT-mediated hypotensive effect.
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Objective@#To analyze the status of serum 25 hydroxyvitamin D[25 (OH)D] in children aged 0-6 years in Gansu Province, and to analyze the relationships between 25 (OH)D and age, seasonal characteristics and physical development, so as to provide a scientific reference for supplementing vitamin D for children in due time.@*Methods@#Stratified random cluster sampling method was used to select a total of 9 790 children aged 0-6 years from 6 cities and prefectures maternity and child health institutions in Gansu Province for health examination from January 2019 to December 2020. Serum 25 (OH)D concentration from 1 mL peripheral blood was tested by enzyme linked immunoassay. Subjects were classified into overweight and normal figure groups based on weight for height.@*Results@#the serum 25 (OH)D level M(P 25 ,P 75 ) of the children aged 0-6 was 81.31(63.14, 95.86)nmol/L. The detection rate of 25 (OH)D deficiency and insufficiency was 45.11%. The serum 25 (OH)D level of children 4- 6 years old was significantly lower than that of infants <1 year old and children 1-<4 years old, and the detection rate of 25 (OH)D deficiency and insufficiency was highest among 4-6 years old( χ 2=83.67, P <0.05). In winter the proportion of 25 (OH)D insufficiency and deficiency was highest (55.82%) ( χ 2=194.12, P <0.01). For overweight children, the abnormal rate of 25 (OH)D (19.83%) was significantly higher in autumn ( P <0.01).@*Conclusion@#Children s vitamin D levels were associated with age, season and physical development. Vitamin D surveillance should be focused on ages less than 1 year old and above 4 years old, winter should be an important season. For overweight children, autumn should be the focus period for vitamin D deficiency prevention.
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Aim To investigate the protective effect of bicyclol on tumor necrosis factor-α/D-galactosamine (TNF-α/D-GalN) induced liver injury and its possible mechanisms. Methods Male C57 mice were given 50, 100, and 200 mg · kg
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Objective To analyze the association of the behaviors of playing mahjong and watching mobile phone with depression in rural women in Hubei Province, so as to provide suggestions for improving their physical and mental health. Methods A stratified cluster sampling method was used to investigate 1367 adult women in 8 administrative villages of 7 counties/cities in Hubei Province. The depression status was measured by the Center for Epidemiological Studies Depression Scale-10 (CESD-10) and the percentage conversion was carried out. The higher the score was, the lower the degree of depression was, and the better the mental health status was. Results The CESD-10 scores of 15-44 years old women（77.63±13.95)were higher than those of 45-64 years old (73.17+17.01) and over 65 years old (69.25+18.16) (P0.05). Conclusions There is a correlation between watching mobile phone and depression of rural women in Hubei Province, reducing the use of mobile phones by rural women, especially middle-aged women, is worthy of attention in the future work of health education and Women’s Federation.
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We evaluate the therapeutic effects of baicalein on chemotherapy-induced intestinal mucositis (CIM) in mice. The role of gut microflora regulation in the therapeutic effects of baicalein was investigated meanwhile. Male Balb/c mice were randomly divided into three groups including normal control group, model group and experimental group. Except for normal control group, mice were injected with 5-fluorouracil and irinotecan to induce CIM. Animal welfare and experimental procedures comply follow the rules of the Animal Ethics Committee of the Institute of Materia Medica, Chinese Academy of Medical Sciences. Baicalein significantly reduced disease activity index (DAI) of CIM mice and decreased the content of interleukin 6 (IL-6) and tumor necrosis factor α (TNF-α) in serum. There were significant differences in the composition of the gut microbiota among groups according to the analysis of α diversity, β diversity, and the species differences. Compared with the normal control group, the Ruminococcaceae_UCG_014 and unclassified_f_Lachnospiraceae in mice of model group were significantly decreased while Bacteroides, Escherichia_Shigella, Enterococcus, Parabacteroides, Clostridium_ sensu_stricto_1, and Lactococcus were significantly increased. Baicalein significantly decreased the abundance of Bacteroides, Escherichia_Shigella, Parabacteroides, Enterococcus, Clostridium_sensu_stricto_1, and Lactococcus. Meantime, norank_f_Muribaculaceae was notably increased by baicalein. The content of IL-6 and TNF-α in the serum of the three groups were positively correlated with the abundance of Clostridium_sensu_ stricto_1, Lactococcus, Bacteroides, and Enterococcus according to correlation analysis. This study suggested the potential therapeutic effect of baicalein on CIM in mice. Regulation of gut microbiota probably plays a critical role in the therapeutic effects of baicalein.
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<p><b>BACKGROUND</b>Transesophageal echocardiography (TEE) is a well-established method for detecting and diagnosing heart tumors. In contrast, its role in assessing the presence, growth and evidence of malignant tumors originating from mediastinal sites remains unclear. The aim of this study was to compare the diagnostic impact of TEE and transthoracic echocardiography (TTE) for determining the localization, growth and malignancy of adult mediastinal tumors (MTs).</p><p><b>METHODS</b>In a prospective and investigator-blinded study, we evaluated 144 consecutive patients with MT lesions to assess the diagnostic impact of TEE and TTE for detecting the presence of tumors spreading both inside and outside of the heart and for determining infiltration and invasion using pathological examination results as a reference.</p><p><b>RESULTS</b>All tumor lesions were diagnosed and carefully evaluated by biopsy. Biopsy revealed malignant tumors in 79 patients and benign tumors in 65 patients. When compared to histological findings, TEE predicted malignancy from the presence of tumors spreading both inside and outside of the heart and from infiltration and invasion in 49/79 patients (62.0%). TTE predicted malignancy in only 8/79 patients (10.1%, P < 0.005). TEE visualized tumor lesions in 130 patients (90.3%) while the TTE visualized tumor lesions in 110 patients (76.4%) and was less effective at detecting MT lesions (P < 0.001). TTE and TEE could detect anterior MTs and adequately verified MTs (P > 0.05); TEE detected medium MTs better than TTE (P < 0.001).</p><p><b>CONCLUSIONS</b>TEE is effective and superior to TTE for predicting the localization and growth of MTs as well as for accessing evidence of tumor malignancy. TTE and TEE were able to detect anterior MTs; TEE was able to detect medium MT better than TTE.</p>
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Adult , Aged , Female , Humans , Male , Middle Aged , Young Adult , Echocardiography, Transesophageal , Methods , Heart Neoplasms , Diagnostic Imaging , Mediastinal Neoplasms , Diagnostic Imaging , Prospective StudiesABSTRACT
Objective: To optimize the technological process for the preparation of curcumin-(oleic acid)2[Cur(OA)2] loaded by mPEG5000-PLGA with modified solvent evaporation method and to characterize the nanoparticles[Cur(OA)2-NPs]. Methods: Using entrapment efficiency (EE), appearance, and particle size as indexes, orthogonal test design was used to optimize the preparation technology. Laser particle size analyzer and transmission electron microscopy (TEM) were carried out to evaluate the Cur(OA)2-NPs size, Zeta potential, and morphological characteristics. Results: The optimal preparation conditions for Cur(OA)2-NPs were as follows: Cur(OA)2-mPEG5000-PLGA (1:4); organic solvent-aqueous solvent (1:2); the stirring speed was 1200 r/min; Poloxamer 188 (F68) concentration was 0.3%. The Cur(OA)2-NPs were spherical and uniformly distributed, with average particle size 86.23 nm (range of particle size: 80-100 nm) and Zeta potential -23.8 mV. Conclusion: The modified solvent evaporation method is suitable to prepare the curcumin derivatives loaded mPEG5000-PLGA NPs.
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<p><b>OBJECTIVE</b>To explore the abnormal expressions of testicular reproduction-related genes induced by glycosides of Tripterygium wilfordii (GTW) and the intervention with kidney-tonifying Chinese herbs.</p><p><b>METHODS</b>Adult Balb/C male mice were fed on GTW at 30 mg per kg per d for 3 weeks to establish a model of reproductive dysfunction. The model mice were divided into different groups to receive intragastrical administration of saline (0.25 ml/d), GTW (30 mg per kg per d), Cistanche (10 g per kg per d), Rehmannia (10 g per kg per d), and Rehmannia + Cistanche (20 g per kg per d), respectively, once a day for 3 weeks. And a Cistanches pretreatment group was treated with GTW (30 mg per kg per d) and Cistanche (10 g per kg per d) for the same length of time. Then we detected the changed expressions of testicular reproduction-related genes Dzip1, Fas, c-jun and Wnt4 in each group.</p><p><b>RESULTS</b>The model mice showed an obviously down-regulated expression of the Y chromosome microdeletion-related gene Dzip1, and up-regulated expressions of the germ cell apoptosis-related gene Fas, proto-oncogene c-jun, and signal transduction-related gene Wnt4. Intervention with Chinese herbs achieved different degrees of improvement of the mice's reproductivity, and the most obvious efficacy was observed with the combined use of kidney-yang tonifying Cistanche and kidney-yin nourishing Rehmannia.</p><p><b>CONCLUSION</b>GTW exerts significant impact on reproduction-related genes. Both the kidney-yang tonifying drug Cistanche and kidney-yin nourishing drug Rehmannia can counteract some of the reproductive toxicity of GTW, while the combination of the two can further enhance the effect.</p>
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Animals , Male , Mice , Cistanche , Drugs, Chinese Herbal , Pharmacology , Glycosides , Pharmacology , Mice, Inbred BALB C , Testis , Metabolism , Tripterygium , ChemistryABSTRACT
<p><b>OBJECTIVE</b>To analyze the clinical characteristics of bone metastasis of malignant tumors.</p><p><b>METHODS</b>The clinical data and survival time of 355 patients with bone metastasis of malignant tumors were retrospectively analyzed.</p><p><b>RESULTS</b>The bone metastasis occurred more frequently in men (male:female = 1.45:1). The most common primary tumors were lung cancer in men and breast cancer in women. The thoracic vertebrae, ribs, lumbar vertebrae and pelvic were frequently involved metastatic sites and the multiple bone metastasis was common (83.4%). The main symptom was pain (75.2%). Local masses, disfunctions, pathologic fracture and paraplegia occurred in a few patients while many patients were asymptomatic (22.0%). The most frequent radiographic manifestation was the osteolytic bone destruction (82.2%). Integrated treatments were taken, including chemotherapy, hormonal therapy, biological therapy, radiotherapy, surgery, bisphosphonate analgetics, etc. The clinical benefit rate in pain relief was 98.5% and the effective rate was 72.2% in radiographic imaging. The median survival time was 13.9 months. Among them, it was 34.9 months in prostate cancer and 4.6 months in hepatocellular carcinoma. The survival time was longer in bone metastasis without other organ metastasis. There was no significant difference between the single and multiple bone metastases regarding the survival time.</p><p><b>CONCLUSION</b>It is important to master the clinical features of bone metastasis of malignant tumors for early diagnosis and treatment, and to improve the quality of life and prolong the survival time.</p>