The association between GAD1 gene polymorphisms and cerebral palsy in Chinese infants

Studies suggest that GAD1 gene was a functional candidate susceptibility gene for cerebral palsy (CP). In order to investigate the contribution of GAD1 gene to the etiology of CP in Chinese infants, we carried out a case-control association study between GAD1 gene and CP. In this study, 374 health controls and 392 infants with CP were recruited. Genomic DNA was extracted from venous blood and all three single nucleotide polymorphisms in GAD1 (rs3791874, rs3791862 and rs16858977) were genotyped by Sequenom’s MassARRAY system. There were no significant differences in allele or genotype frequencies between CP or mixed CP patients and controls at any of the three genetic polymorphisms. Through haplotype analysis we found that haplotype GG (rs3791862, rs16858977) frequency demonstrated significantly statistical difference between mixed CP patients and controls (p= 0.0371). Our positive findings of haplotype GG suggested that variation of GAD1 gene was an important risk factor for mixed CP.Предполагается, что ген GAD1 является функциональным кандидатом на роль гена подверженности церебральному параличу (ЦП). Для исследования вклада гена GAD1 в этиологию ЦП у китайских детей методом случай – контроль проведено исследование ассоциации между наличием гена GAD1 и ЦП. В исследовании были задействованы 374 здоровых ребенка (контроль) и 392 ребенка с ЦП. Геномную ДНК выделяли из венозной крови, и все три единичных нуклеотидных полиморфизма гена GAD1 (rs3791874, rs3791862 и rs16858977) были генотипированы в системе Sequenom MassARRAY. Ни для одного из трех генетических полиморфизмов не обнаружено существенных различий в частотах аллелей или генотипов между больными ЦП или смешанными больными ЦП и контролем. Анализ гаплотипов показал существенные статистические различия в частоте гаплотипа GG (rs3791862, rs16858977) у смешанных больных ЦП и контрольной группы (p = 0.0371). Позитивный результат по гаплотипу GG свидетельствует о том, что вариация гена GAD1 является важным фактором риска для смешанного ЦП

Large expert-curated database for benchmarking document similarity detection in biomedical literature search

Document recommendation systems for locating relevant literature have mostly relied on methods developed a decade ago. This is largely due to the lack of a large offline gold-standard benchmark of relevant documents that cover a variety of research fields such that newly developed literature search techniques can be compared, improved and translated into practice. To overcome this bottleneck, we have established the RElevant LIterature SearcH consortium consisting of more than 1500 scientists from 84 countries, who have collectively annotated the relevance of over 180 000 PubMed-listed articles with regard to their respective seed (input) article/s. The majority of annotations were contributed by highly experienced, original authors of the seed articles. The collected data cover 76% of all unique PubMed Medical Subject Headings descriptors. No systematic biases were observed across different experience levels, research fields or time spent on annotations. More importantly, annotations of the same document pairs contributed by different scientists were highly concordant. We further show that the three representative baseline methods used to generate recommended articles for evaluation (Okapi Best Matching 25, Term Frequency-Inverse Document Frequency and PubMed Related Articles) had similar overall performances. Additionally, we found that these methods each tend to produce distinct collections of recommended articles, suggesting that a hybrid method may be required to completely capture all relevant articles. The established database server located at https://relishdb.ict.griffith.edu.au is freely available for the downloading of annotation data and the blind testing of new methods. We expect that this benchmark will be useful for stimulating the development of new powerful techniques for title and title/abstract-based search engines for relevant articles in biomedical research.Peer reviewe

All-trans retinoic acid inhibits the malignant behaviors of hepatocarcinoma cells by regulating ferroptosis

All-trans retinoic acid (ATRA) can reverse the malignant behaviors of hepatocellular carcinoma (HCC) cells, thereby exerting anti-HCC effect; however, the underlying mechanism is yet to be understood. This study aimed to demonstrate that ATRA is vital to ferroptosis in HCC. Ferroptosis-related genes exhibit different expression in patients with HCC compared to that in healthy individuals. A total of 20 amino acid products were detected in HepG2 cells, the expression level of 5 was decreased after ATRA treatment. ATRA improved the levels of lipid ROS, MDA, and NAPD+/NADPH, and reduced the mt-DNA copy number and changed the structure of mitochondria, in HepG2 and Hep3B cells. We found the expression of genes positively correlated with ferroptosis to increase and those negatively correlated to decrease with ATRA treatment. Inhibition of ferroptosis by Ferrostatin-1 reversed ATRA-inhibited proliferation of HCC cells, along with cell migration and invasion. GSH synthesis was blocked by ATRA, accompanied by decreased cystine content and increased glutamate content, and downregulation of the expression of GSH synthesis-related genes. Our findings suggested that ATRA inhibited the malignancy of HCC cells by improving ferroptosis, and that inhibition of GSH synthesis contributed to ATRA-induced ferroptosis

LncRNA ITGB2-AS1 Could Promote the Migration and Invasion of Breast Cancer Cells through Up-Regulating ITGB2

In the previous study, we screened a novel lncRNA-ITGB2-AS1, which was down-regulated by bone morphogenetic protein 9 (BMP9) in breast cancer cell. Studying ITGB2-AS1 will lay the foundation for the exploring mechanism of the BMP9 inhibitory effect on breast cancer. The expression analysis related to ITGB2-AS1 in clinical samples was conducted on online websites. The overexpression plasmid or siRNA fragment was transfected into breast cancer cells to alter its gene expression. The MTT assay and flow cytometry were used to measure cell viability and cell cycle. Additionally, cell migration and invasion were detected by wound healing and transwell assay. The results of biological function experiments showed that ITGB2-AS1 could promote the migration and invasion of breast cancer. Furthermore, ITGB2-AS1 increased the mRNA and protein expression of ITGB2. Consistent with ITGB2-AS1, ITGB2 exerted the promotion effect on the migration and invasion of breast cancer and activated integrin-related FAK signaling. The OL plasmid expressing the truncation of ITGB2-AS1, which was complementary to ITGB2, was essential for activation of FAK signaling. In conclusion, LncRNA ITGB2-AS1 could promote the migration and invasion of breast cancer cells by up-regulating ITGB2

Activation of PKA/CREB Signaling is Involved in BMP9-Induced Osteogenic Differentiation of Mesenchymal Stem Cells

Background/Aims: BMP9 is highly capable of promoting osteogenic differentiation of mesenchymal stem cells (MSCs) although the molecular mechanism involved is largely unknown. Here, we explored the detail role of PKA/CREB signaling in BMP9-induced osteogenic differentiation. Methods: Activation status of PKA/CREB signaling is assessed by nonradioactive assay and Western blot. Using PKA inhibitors and a dominant negative protein of CREB (A-CREB), we investigated the effect of PKA/CREB signaling on BMP9-induced osteogenic differentiation. Results: We found that BMP9 promotes PKA activity and enhances CREB phosphorylation in MSCs. BMP9 is shown to down-regulate protein kinase A inhibitor γ (PKIγ) expression. We demonstrated that PKA inhibitors suppress BMP9-induced early osteogenic marker alkaline phosphatase (ALP) activity in MSCs as well as late osteogenic markers osteopontin (OPN), osteocalcin (OCN) and matrix mineralization. We found that PKA inhibitor reduces BMP9-induced Runx2 activation and p38 phosphorylation in MSCs. Lastly, interference of CREB function by A-CREB decreased BMP9-induced osteogenic differentiation as well. Conclusion: Our results revealed that BMP9 may activate PKA/CREB signaling in MSCs through suppression of PKIγ expression. It is noteworthy that inhibition of PKA/CREB signaling may impair BMP9-induced osteogenic differentiation of MSCs, implying that activation of PKA/CREB signaling is required for BMP9 osteoinductive activity

BMP9 Promotes the Proliferation and Migration of Bladder Cancer Cells through Up-Regulating lncRNA UCA1

As the most common malignant tumor of the urinary system worldwide, the bladder tumor has a high mortality rate, which is mainly due to its onset of concealment. Therefore, research into novel diagnostic markers and treatment of bladder cancer is urgently needed. BMP9 (Bone morphogenetic protein 9) is a member of BMP, which belongs to the TGF-β (transforming growth factor-β) superfamily. It has been associated with multiple tumors. We found that BMP9 is highly expressed in bladder cancer cells and it could significantly promote the proliferation and migration of bladder cancer cells. In the study of the mechanism of this effect, we found that BMP9 can increase the expression of lncRNA UCA1 (Urothelial cancer associated 1) through phosphorylated AKT. The promoting effect of BMP9 on bladder cancer cells was rescued after interfering with UCA1 in BMP9 overexpressed bladder cancer cells both in vitro and in vivo. Our research confirms that BMP9 promotes the proliferation and migration of bladder cancer cells through up-regulated lncRNA UCA1. It also shows that BMP9 is a novel diagnostic marker and a potential therapeutic target in bladder cancer

Quality Distinguish of Red Ginseng from Different Origins by HPLC–ELSD/PDA Combined with HPSEC–MALLS–RID, Focus on the Sugar-Markers

Red ginseng (RG) has been extensively utilized in Asian countries due to its pharmacological effects. For the quality evaluation of RG, small molecules, such as ginsenosides, have been widely considered as candidates of its quality markers (Q-markers), and various analytical techniques have been developed in order to identify these compounds. However, despite the efforts to analyze the hydrophobic constituents, it is worth pointing out that about 60% of the mass of RG is made of carbohydrates, including mono-, oligo- and polysaccharides. Consequently, the quality differentiation and identification of RG from the perspective of sugar-markers should be focused. High performance liquid chromatography and evaporative light scattering detector (HPLC–ELSD) method for the determination of disaccharides in RG was established. Furthermore, high performance size exclusion chromatography–multi-angle laser light scattering–refractive index detector (HPSEC–MALLS–RID) for the determination of molecular weight and high performance liquid chromatography photodiode array (HPLC–PDA) for the determination of compositional monosaccharides in RG polysaccharides were also established. HPLC–ELSD/PDA combined with HPSEC–MALLS–RID could be used to determine the contents of disaccharides, molecular weights, and compositional monosaccharides of RG polysaccharides, which could be used for quality control, and this is a new view on the sugar marker to quality differentiation of various origins of RG

Three-Dimensional Reconstruction of Computed Tomography Imaging Is Not Reliable in Assessing Acetabular Rim Osteophytes or Acetabular Rim Pathology in Patients With Femoroacetabular Impingement

Purpose: To determine the reliability of 3-dimensional (3D) reconstruction of computed tomography (CT) imaging in evaluating acetabular rim morphology or acetabular rim osteophyte (ARO) existence and to group patients with femoroacetabular impingement (FAI) by ARO extent on coronal sections of CT and further compare clinical differences among groups. Methods: Patients who underwent primary hip arthroscopy for FAI by the same surgeon between August 2016 and December 2018 with minimum 2-year follow-up were enrolled. The ARO was evaluated both on the acetabular gross anatomy (AGA) and coronal sections of CT, for its position, width (unit: mm), area (unit: mm2), and CT value (unit: HU). Patients were divided into 4 groups based on the extent of ARO on coronal CT: group A (ARO anterior to 12 o’clock), group P (ARO posterior to 12 o’clock), group AP (ARO across 12 o’clock), and group N (no ARO). Inter- and intraobserver correlation was analyzed. Demographic data, FAI deformity indicators on imaging, quantitative measurements of ARO, and pre- and postoperative patient-reported outcomes were compared among groups. Results: There were 229 patients (229 hips) enrolled in total, 122 male (53.3%) and 107 female (46.7%), with a mean age of 37.2 ± 10.2 years. The correlation between 2 observers for grouping ARO using AGA was positive but poor (Kendall Tau-b coefficient = 0.157, P = .008). Moderate correlation was found between grouping based on AGA and coronal CT by the same observer (Kendall Tau-b coefficient = 0.482, P = .000). The patients were divided into 4 groups: 84 patients (36.7%) in group N, 2 patients (0.9%) in group A, 69 patients (30.1%) in group P, and 74 patients (32.3%) in group AP. Group N was younger in age (35.4 ± 10.7 years) than group P (39.6 ± 10.2 years) (P = 0.012) and had a larger proportion of women (57.1%) than group AP (36.5%) (χ2 = 6.869, P = .032). There was a greater proportion of positive posterior wall sign in group P (52.2%) than 48.6% for group AP and 33.3% for group N (χ2 = 6.397, P = .041). Group N had 61 (72.6%) Tönnis grade 0 hips compared with 37 (50%) in group AP (P = .014). No statistical significance was found among groups in pre- and postoperative α angle, lateral center-edge angle, and patient-reported outcomes. The widths of ARO in group AP for the 3 marked points from anterior to posterior were 3.88 ± 1.86, 4.84 ± 2.72, and 6.66 ± 3.18, separately (P＜.001); 15.73 ± 21.46, 19.22 ± 18.86, and 29.96 ± 17.05 for area (P＜.01); and 652.67 ± 214.12, 677.10 ± 274.81, and 728.84 ± 232.39 for CT value (P＜.05). For the ARO posterior to 12 o’clock, the group AP showed a larger width (6.66 ± 3.18), area (29.96 ± 17.05), and CT value (728.84 ± 232.39) than group P of (4.70 ± 2.25), (20.15 ± 12.91), and (641.84 ± 183.33) (P＜.001). Conclusions: The evaluation of ARO on AGA is poor consistent with definite double-rim sign on coronal CT. There is a tendency of size-enlarging and density-increasing for ARO from anterior to posterior along the acetabular rim. Younger age, female gender, lower Tönnis grade, and negative posterior wall sign showed lower rate of ARO development. Level of Evidence: Level IV, diagnostic case series

Improving Magnetofection of Magnetic Polyethylenimine Nanoparticles into MG-63 Osteoblasts Using a Novel Uniform Magnetic Field

Abstract This study aimed to improve the magnetofection of MG-63 osteoblasts by integrating the use of a novel uniform magnetic field with low molecular weight polyethylenimine modified superparamagnetic iron oxide nanoparticles (PEI-SPIO-NPs). The excellent characteristics of PEI-SPIO-NPs such as size, zeta potential, the pDNA binding and protective ability were determined to be suitable for gene delivery. The novel uniform magnetic field enabled polyethylenimine-modified superparamagnetic iron oxide nanoparticles/pDNA complexes (PEI-SPIO-NPs/pDNA complexes) to rapidly and uniformly distribute on the surface of MG-63 cells, averting local transfection and decreasing disruption of the membrane caused by the centralization of positively charged PEI-SPIO-NPs, thereby increasing the effective coverage of magnetic gene carriers during transfection, and improving magnetofection efficiency. This innovative uniform magnetic field can be used to determine the optimal amount between PEI-SPIO-NPs and pDNA, as well as screen for the optimal formulation design of magnetic gene carrier under the homogenous conditions. Most importantly, the novel uniform magnetic field facilitates the transfection of PEI-SPIO-NPs/pDNA into osteoblasts, thereby providing a novel approach for the targeted delivery of therapeutic genes to osteosarcoma tissues as well as a reference for the treatment of other tumors