Inhibition of the ITGB1 gene attenuates crystalline silica-induced pulmonary fibrosis via epithelial-mesenchymal transformation

Silicosis is a systemic disease caused by long-term exposure to high concentrations of free silica dust particles in the workplace. It is characterized by a persistent inflammatory response, fibroblast proliferation, and excessive collagen deposition, leading to pulmonary interstitial fibrosis. Epithelial interstitial transformation (EMT) can cause epithelial cells to lose their tight junctions, cell polarity, and epithelial properties, thereby enhancing the properties of interstitial cells, which can lead to the progression of fibrosis and the formation of scar tissue. Integrin 1 (ITGB1) is considered an important factor for promoting EMT and tumor invasion in a variety of tumors and also plays an important role in the progression of fibrotic diseases. Therefore, ITGB1 can be used as a potential target for the treatment of silicosis. In this study, we found that silica exposure induced epithelial-mesenchymal transformation in rats and that the expression of integrin ITGB1 was elevated along with the EMT. We used CRISPR/Cas9 technology to construct integrin ITGB1 knockdown cell lines for in vitro experiments. We compared the expression of the EMT key proteins E-cadherin and vimentin in the ITGB1 knockdown cells and wild-type cells simultaneously stimulated by silica and detected the aggregation point distribution of E-cadherin and vimentin in the cells using laser confocal microscopy. Our results showed that ITGB1 knockout inhibited the ITGB1/ILK/Snail signaling pathway and attenuated the EMT occurrence compared to control cells. These results suggested that ITGB1 is associated with silica-induced EMT and may be a potential target for the treatment of silicosis.

RhoGEF Trio Regulates Radial Migration of Projection Neurons via Its Distinct Domains / 神经科学通报·英文版

The radial migration of cortical pyramidal neurons (PNs) during corticogenesis is necessary for establishing a multilayered cerebral cortex. Neuronal migration defects are considered a critical etiology of neurodevelopmental disorders, including autism spectrum disorders (ASDs), schizophrenia, epilepsy, and intellectual disability (ID). TRIO is a high-risk candidate gene for ASDs and ID. However, its role in embryonic radial migration and the etiology of ASDs and ID are not fully understood. In this study, we found that the in vivo conditional knockout or in utero knockout of Trio in excitatory precursors in the neocortex caused aberrant polarity and halted the migration of late-born PNs. Further investigation of the underlying mechanism revealed that the interaction of the Trio N-terminal SH3 domain with Myosin X mediated the adherence of migrating neurons to radial glial fibers through regulating the membrane location of neuronal cadherin (N-cadherin). Also, independent or synergistic overexpression of RAC1 and RHOA showed different phenotypic recoveries of the abnormal neuronal migration by affecting the morphological transition and/or the glial fiber-dependent locomotion. Taken together, our findings clarify a novel mechanism of Trio in regulating N-cadherin cell surface expression via the interaction of Myosin X with its N-terminal SH3 domain. These results suggest the vital roles of the guanine nucleotide exchange factor 1 (GEF1) and GEF2 domains in regulating radial migration by activating their Rho GTPase effectors in both distinct and cooperative manners, which might be associated with the abnormal phenotypes in neurodevelopmental disorders.

Role of microRNAs in erectile dysfunction: An update / 中华男科学杂志

MicroRNAs (miRNAs) are short non-coding RNAs consisting of approximately 19－23 nucleotides and involved in many pathological and physiological processes by regulating post-transcriptional gene expressions. ED is one of the common male sexual dysfunctions seriously affecting the patient's quality of life, for which there is currently a lack of effective treatments clinically. More and more experiments have demonstrated that miRNAs are involved in the pathological process of different types of ED. This article presents an overview of the progress in the studies of the pathogenic role of miRNAs in ED.

Losartan improves erectile function through suppression of corporal apoptosis and oxidative stress in rats with cavernous nerve injury / 亚洲男科学杂志(英文版)

This study aimed to investigate the functional and morphological changes in the corpus cavernosum after cavernous nerve (CN) injury or neurectomy and then reveal whether treatment with the angiotensin II Type 1 receptor antagonist losartan would improve erectile function as well as its potential mechanisms. A total of 48 10-week-old Sprague-Dawley male rats, weighing 300-350 g, were randomly divided into the following four groups (n = 12 per group): sham operation (Sham) group, bilateral cavernous nerve injury (BCNI) group, losartan-treated BCNI (BCNI + Losartan) group, and bilateral cavernous neurectomy (Neurectomy) group. Losartan was administered once daily by oral gavage at a dose of 30 mg kg-1 day-1 for 4 weeks starting on the day of surgery. The BCNI and the Neurectomy groups exhibited decreases in erectile response and increases in apoptosis and oxidative stress, compared with the Sham group. Treatment with losartan could have a modest effect on erectile function and significantly prevent corporal apoptosis and oxidative stress. The phospho-B-cell lymphoma 2 (Bcl-2)-associated death promoter (p-Bad)/Bad and phospho-the protein kinase B (p-AKT)/AKT ratios were substantially lower, while the Bcl-2-associated X protein (Bax)/Bcl-2 ratio, nuclear factor erythroid 2-related factor 2 (Nrf2)/Kelch-like ECH-associated protein 1 (Keap-1), transforming growth factor-β 1 (TGF-β 1) and heme oxygenase-1 (HO-1) levels, and caspase-3 activity were higher in the BCNI and Neurectomy groups than in the Sham group. After 4 weeks of daily administration with losartan, these expression levels were remarkably attenuated compared with the BCNI group. Taken together, our results suggested that early administration of losartan after CN injury could slightly improve erectile function and significantly reduce corporal apoptosis and oxidative stress by inhibiting the Akt/Bad/Bax/caspase-3 and Nrf2/Keap-1 pathways.

Thermal Desorption-Gas Chromatography or Gas Chromatograph-Mass Spectrometry for Analysis of Semi-Volatile Compounds on Atmospheric Particulate Matters / 分析化学

A thermal desorption ( TD) device was developed and coupled to gas chromatography ( GC) or gas chromatography-mass spectrometry ( GC-MS ) for the qualitative and quantitative analysis of semi-volatile organic compounds on atmospheric particulate matters ( PM ) . The TD was operated by direct heating and placed on the GC injector, leading to high heating rate and easy transfer of analytes to GC without focusing of analytes by cold trap. For establishing the TD-GC method, the materials used for supporting PM samples, temperature and time of thermal desorption, and types of sample injection were investigated for detection of sixteen polycyclic aromatic hydrocarbons ( PAHs) and nine n-alkanes. The limits of detection of the proposed TD-GC method were in the range of 0. 014-0. 093 ng for PAHs, and 0. 016-0. 026 ng for n-alkanes, respectively, with the correlation coefficients of correlation above 0. 9975. The TD-GC method was applied to the determination of trace PAHs and n-alkanes on PM10 samples from three cities. The recoveries were in the range of 95%-135% ( PAHs) and 95%-115% ( n-alkanes) , respectively. Finally, the TD was coupled to GC-MS for comparison of the contents of PAHs and n-alkanes on PMx with different particulate size ( x=10 , 5, 2, 1, 0. 5, 0. 25, 0. 1).

Application of the modulation transfer function to evaluate the early visual quality after full femtosecond laser refractive surgery / 中华实验眼科杂志

Background Full femtosecond laser refractive surgery has been generally applied,but the improvement of visual quality after surgery is a vital problem.It is well-known that modulation transfer function (MTF) is a major evaluation indicator.Objective To investigate the change of the MTF of operated eyes after the full femtosecond laser refractive surgery.Methods A retrospective series of cases study was adopted.Forty eyes of 23 patients with the spherical equivalent of-2.25 to-5.75 D who received full femtosecond laser refractive surgery were enrolled in Nanjing General Hospital of Nanjing Military Command from July to October,2012.The change of visual acuities was analyzed and compared among before operation and 1 day,1 week and 1 month after operation.MTF value in total aberration,low and high order aberrations under the 3.0 mm and 6.0 mm pupil size conditions were detected with i-Trace Visual Function Analyzer at above time points.The MTF values among various time points,between different pupil diameters and different spatial frequencies (5,10,15,20,25 c/d) were compared respectively.Results Compared with the preoperation,the visual acuity improved in postoperative 1 day,1 week and 1 month,showing a significant improvement among various time points (F =10.341,P =0.000).Corrected diopter was 3.795 D at average.MTF values under the 3 mm pupil diameter gradually elevated with the lapse of time after operation,without significant differences among different time points whatever total aberration,low and high order aberrations(all at P＞0.05).The MTF values under 6 mm pupil diameter of total aberration and low order aberration were significantly higher in postoperation than those in preoperation(all at P＜0.05),but no significant difference was seen in MTF of high order aberration among various time points (F =0.260,P =0.854).Compared with the MTF under the 3 mm pupil diameter,those of low and high order aberrations under the 6 mm pupil diameter considerably declined in preoperation and postoperative 1 month (preoperation:P =0.050,0.001 ; postoperation:P =0.012,0.001).MTF values under the 3 mm pupil diameter were not different at various spatial frequencies (all at P＞ 0.05).However,MTF values under the 6 mm pupil diameter were gradually increased from preoperation through postoperative 1 month at 10,15,20 and 25 c/d (P =0.044,0.043,0.024,0.014).Conclusions Full femtosecond laser refractive surgery can eliminate low aberration,increase the MTF and acuity,and therefore improve the visual quality.MTF is one of the key indicators assessing visual quality after full femtosecond laser refractive surgery.

In vivo study of antifertility and anti-inflammatory effects of compound Kucen gel / 中华男科学杂志

<p><b>OBJECTIVE</b>To study the antifertility and anti-inflammatory effects of compound Kucen gel in vivo.</p><p><b>METHODS</b>As antifertility experiment, we randomly divided 60 female SD rats into six groups of equal number: normal saline, blank gel, low-, medium- and high-dose compound Kucen gel (0.05, 0.10 and 0.15 g/g), and positive control (4% nonoxynol gel) to receive intravaginal administration of 200 microl of respective agent, followed by copulation with male rats in a 1:1 ratio. At 12 days after successful mating, the female rats were dissected for calculation of the embryos and the rate of contraception. As an anti-inflammatory trial, we established a mouse model of inflammation by applying xylene to the pinna, and equally randomized 60 Kunming mice to six groups as in the former experiment. We determined the degrees and average rates of swelling inhibition in the left ear.</p><p><b>RESULTS</b>High-dose compound Kucen gel achieved a fertility-inhibition rate of 100% in the female rats, the number of embryos significantly lower than in the normal saline group (0.00 +/- 0.00 vs 11.00 +/- 2. 00, P < 0.05), but with no statistically insignificant difference from that of the positive control (0.00 +/- 0.00, P > 0.05). High-dose compound Kucen gel also markedly suppressed swelling in the left ear of the mice, with an inhibition rate of 52.3%, the average swelling degree significantly lower than in the normal saline group (10.17 +/- 2.56 vs 21.32 +/- 3.17, P < 0.01), but not remarkably different from that of the positive control (8.53 +/- 1.89, P > 0.05).</p><p><b>CONCLUSION</b>Compound Kucen gel, with its strong antifertility and anti-inflammatory effects, deserves further study and clinical application.</p>

Spermicidal effect of alcohol extracts from different ratios of Sophora flavescens Ait/Chinese Bulbul in vitro / 中华男科学杂志

<p><b>OBJECTIVE</b>To observe the spermicidal effect of alcohol extracts from different ratios of Sophora flavescens Ait/Chinese Bulbul in vitro.</p><p><b>METHODS</b>Semen samples aseptically obtained by masturbation and prepared by density gradient centrifugation from 15 healthy men were incubated in the alcohol extracts from 9 different ratios of Sophora flavescens Ait/Chinese Bulbul for 20 seconds, 2 minutes and 4 minutes. Then the motility and movement parameters of the sperm were detected by computer-assisted semen analysis, and the minimal effective concentrations of the instant spermicidal effect of the extracts were determined.</p><p><b>RESULTS</b>At the ratio of 3:1, the extract at 0.5 mg/ml significantly inhibited the sperm motility and other sperm movement parameters VCL, VSL, VAP, ALH, WOB and MAD, as compared with the control group. The minimal effective concentration of the instant spermicidal effect of the extracts was 3.5 mg/ml at 3:1.</p><p><b>CONCLUSION</b>The alcohol extracts from Sophora flavescens Ait and Chinese Bulbul at the ratio of 3:1 have the best spermicidal effect in vitro.</p>

Optimization of transfection efficiency of small interfering RNA in purified human prolactinoma cells / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>Control of hypersecretion of certain hormones is one of the key targets in the treatment of pituitary adenomas. RNA interference has been shown to inhibit protein expression, and thus it may represent a promising method for the treatment of pituitary adenomas. In the present study, transfection efficiency of small interfering RNA (siRNA) was optimized in human prolactinoma cells.</p><p><b>METHODS</b>First, a method was optimized to extract highly purified human prolactinoma cells in vitro. The extracted cells were verified to retain the physiological features of prolactin (PRL) secretion. Second, three conditions for siRNA transfection were tested by the evaluation of transfection efficiency and cell viability. The proper transfection condition was verified for human prolactinoma cells. Third, the siRNA for prolactin was transfected into the human prolactinoma cells, and the suppression of PRL mRNA was evaluated by quantitative real-time reverse transcription-PCR.</p><p><b>RESULTS</b>The siRNA of 100 pmol with Lipofectamine 2000 of 5 µl for 1 × 10(6) cells was proved preferable, with transfection efficiency being 53.3% and cell viability being 69.7%. In the preliminary experiment the siRNA against PRL decreased the mRNA of PRL by 34.0%.</p><p><b>CONCLUSION</b>It is possible to inhibit hormone hypersecretion by RNA interference, that may eventually enable therapeutic siRNA drugs developed.</p>

Study on prognostic factors of chronic severe hepatitis / 中华实验和临床病毒学杂志

<p><b>OBJECTIVE</b>To analyze factors influencing prognosis and to develop a prognosis predicting model for patients with chronic severe hepatitis.</p><p><b>METHODS</b>Clinical data from 408 patients suffering from chronic severe hepatitis were divided into improved group and deteriorated group. The main clinical and laboratory variables were analyzed as predictive factors of prognosis with logistic regression analysis.</p><p><b>RESULTS</b>It was shown that age, sex, TBil, DBil, [Cl-], [Na+], WBC, MCV, PT, NH3, PTA, and BUN were different between the two groups with statistical significance (P < 0.05). The prognosis predicting model was P = 1/(1 + e(-y)), Y = -4.636 + 0.022X1 + 0.034X2 + 0.096X3 + 0.047X4 - 0.042X5, (X1-age, X2-TBil, X3-BUN, X4-MCV, X5-PTA).</p><p><b>CONCLUSION</b>Age, TBil, BUN, MCV and PTA are the independent risk factors related to prognosis of chronic severe hepatitis.</p>