Telomerase-related advances in hepatocellular carcinoma: A bibliometric and visual analysis.

BACKGROUND: As a critical early event in hepatocellular carcinogenesis, telomerase activation might be a promising and critical biomarker for hepatocellular carcinoma (HCC) patients, and its function in the genesis and treatment of HCC has gained much attention over the past two decades. AIM: To perform a bibliometric analysis to systematically assess the current state of research on HCC-related telomerase. METHODS: The Web of Science Core Collection and PubMed were systematically searched to retrieve publications pertaining to HCC/telomerase limited to "articles" and "reviews" published in English. A total of 873 relevant publications related to HCC and telomerase were identified. We employed the Bibliometrix package in R to extract and analyze the fundamental information of the publications, such as the trends in the publications, citation counts, most prolific or influential writers, and most popular journals; to screen for keywords occurring at high frequency; and to draw collaboration and cluster analysis charts on the basis of coauthorship and co-occurrences. VOSviewer was utilized to compile and visualize the bibliometric data. RESULTS: A surge of 51 publications on HCC/telomerase research occurred in 2016, the most productive year from 1996 to 2023, accompanied by the peak citation count recorded in 2016. Up to December 2023, 35226 citations were made to all publications, an average of 46.6 citations to each paper. The United States received the most citations (n = 13531), followed by China (n = 7427) and Japan (n = 5754). In terms of national cooperation, China presented the highest centrality, its strongest bonds being to the United States and Japan. Among the 20 academic institutions with the most publications, ten came from China and the rest of Asia, though the University of Paris Cité, Public Assistance-Hospitals of Paris, and the National Institute of Health and Medical Research (INSERM) were the most prolific. As for individual contributions, Hisatomi H, Kaneko S, and Ide T were the three most prolific authors. Kaneko S ranked first by H-index, G-index, and overall publication count, while Zucman-Rossi J ranked first in citation count. The five most popular journals were the World Journal of Gastroenterology, Hepatology, Journal of Hepatology, Oncotarget, and Oncogene, while Nature Genetics, Hepatology, and Nature Reviews Disease Primers had the most citations. We extracted 2293 keywords from the publications, 120 of which appeared more than ten times. The most frequent were HCC, telomerase and human telomerase reverse transcriptase (hTERT). Keywords such as mutational landscape, TERT promoter mutations, landscape, risk, and prognosis were among the most common issues in this field in the last three years and may be topics for research in the coming years. CONCLUSION: Our bibliometric analysis provides a comprehensive overview of HCC/telomerase research and insights into promising upcoming research.

Predictors of Gleason Grading Group Upgrading in Low-Risk Prostate Cancer Patients From Transperineal Biopsy After Radical Prostatectomy.

RATIONALE AND OBJECTIVES: To investigate the predictors of Gleason Grading Group (GGG) upgrading in low-risk prostate cancer (Gleason score=3 + 3) from transperineal biopsy after radical prostatectomy (RP). MATERIALS AND METHODS: The clinical data of 160 patients who underwent transperineal biopsy and RP from January 2017 to December 2022 were retrospectively analyzed. First, univariate and multivariate logistic regression analysis were used to obtain independent predictors of postoperative GGG upgrading. Then receiver operating characteristic curve was used to evaluate the diagnostic efficacy of predictors. Finally, Linear-by-Linear Association test was used to analyze the risk trends of patients in different predictor groups in the postoperative GGG. RESULTS: In this study, there were 81 cases (50.6%) in the GGG concordance group and 79 cases (49.4%) in the GGG upgrading group. Univariate analysis showed age, free/total prostate-specific antigen (f/tPSA), proportion of positive biopsies, positive target of magnetic-resonance imaging (MRI) and positive target of contrast-enhanced ultrasound had significant effects on GGG upgrading (all P < .05). In multivariate logistic regression analysis, age (odds ratio [OR]=1.066, 95%CI=1.007-1.127, P = .027), f/tPSA (OR=0.001, 95%CI=0-0.146, P = .001) and positive target of MRI (OR=3.005, 95%CI=1.353-76.674, P = .007) were independent predictors. The prediction model (area under curve=0.751 P < .001) had higher predictive efficacy than all independent predictors. The proportion of patients in exposed group of different GGG increased with the level of GGG, but decreased in nonexposed group, and the linear trend was significantly different (all P < .001). CONCLUSION: Age, f/tPSA, and positive target of MRI were independent predictors of postoperative GGG upgrading. The predictive model constructed had the best diagnostic efficacy.

High spindle and kinetochore-associated complex subunit-3 expression predicts poor prognosis and correlates with adverse immune infiltration in hepatocellular carcinoma.

BACKGROUND: Spindle and kinetochore-associated complex subunit 3 (SKA3) is a malignancy-associated gene that plays a critical role in the regulation of chromosome separation and cell division. However, the molecular mechanism through which SKA3 regulates tumor cell proliferation in hepatocellular carcinoma (HCC) has not been fully elucidated. AIM: To investigate the molecular mechanisms underlying the role of SKA3 in HCC. METHODS: SKA3 expression, clinicopathological, and survival analyses were performed using multiple public database platforms, and the results were verified by Western blot and immunohistochemistry staining using collected clinical samples. Functional enrichment analyses were performed to evaluate the biological functions and molecular mechanisms of SKA3 in HCC. Furthermore, the Tumor Immune Estimation Resource and single-sample Gene Set Enrichment Analysis (ssGSEA) algorithms were utilized to investigate the abundance of tumor-infiltrating immune cells in HCC. The response to chemotherapeutic drugs was evaluated by the R package "pRRophetic". RESULTS: We found that upregulated SKA3 expression was significantly correlated with poor prognosis in patients with HCC. Multivariable Cox regression analysis indicated that SKA3 was an independent risk factor for survival. GSEA revealed that SKA3 expression may facilitate proliferation and migratory processes by regulating the cell cycle and DNA repair. Moreover, patients with high SKA3 expression had significantly decreased ratios of CD8+ T cells, natural killer cells, and dendritic cells. Drug sensitivity analysis showed that the high SKA3 group was more sensitive to sorafenib, sunitinib, paclitaxel, doxorubicin, gemcitabine, and vx-680. CONCLUSION: High SKA3 expression led to poor prognosis in patients with HCC by enhancing HCC proliferation and repressing immune cell infiltration surrounding HCC. SKA3 may be used as a biomarker for poor prognosis and as a therapeutic target in HCC.

Enthalpy and entropy synergistic regulation-based programmable DNA motifs for biosensing and information encryption.

Deoxyribonucleic acid (DNA) provides a collection of intelligent tools for the development of information cryptography and biosensors. However, most conventional DNA regulation strategies rely solely on enthalpy regulation, which suffers from unpredictable stimuli-responsive performance and unsatisfactory accuracy due to relatively large energy fluctuations. Here, we report an enthalpy and entropy synergistic regulation-based pH-responsive A+/C DNA motif for programmable biosensing and information encryption. In the DNA motif, the variation in loop length alters entropic contribution, and the number of A+/C bases regulates enthalpy, which is verified through thermodynamic characterizations and analyses. On the basis of this straightforward strategy, the performances, such as pKa, of the DNA motif can be precisely and predictably tuned. The DNA motifs are finally successfully applied for glucose biosensing and crypto-steganography systems, highlighting their potential in the field of biosensing and information encryption.

Diagnostic performance of artificial intelligence-based computer-aided diagnosis system in longitudinal and transverse ultrasonic views for differentiating thyroid nodules.

Objective: To evaluate the diagnostic performance of different ultrasound sections of thyroid nodule (TN) using computer-aided diagnosis system based on artificial intelligence (AI-CADS) in predicting thyroid malignancy. Materials and methods: This is a retrospective study. From January 2019 to July 2019, patients with preoperative thyroid ultrasound data and postoperative pathological results were enrolled, which were divided into two groups: lower risk group (ACR TI-RADS 1, 2 and 3) and higher risk group (ACR TI-RADS 4 and 5). The malignant risk scores (MRS) of TNs were obtained from longitudinal and transverse sections using AI-CADS. The diagnostic performance of AI-CADS and the consistency of each US characteristic were evaluated between these sections. The receiver operating characteristic (ROC) curve and the Cohen κ-statistic were performed. Results: A total of 203 patients (45.61 ± 11.59 years, 163 female) with 221 TNs were enrolled. The area under the ROC curve (AUC) of criterion 3 [0.86 (95%CI: 0.80~0.91)] was lower than criterion 1 [0.94 (95%CI: 0.90~ 0.99)], 2 [0.93 (95%CI: 0.89~0.97)] and 4 [0.94 (95%CI: 0.90, 0.99)] significantly (P<0.001, P=0.01, P<0.001, respectively). In the higher risk group, the MRS of transverse section was higher than longitudinal section (P<0.001), and the agreement of extrathyroidal extension and shape was moderate and fair (κ =0.48, 0.31 respectively). The diagnostic agreement of other ultrasonic features was substantial or almost perfect (κ >0.60). Conclusion: The diagnostic performance of computer-aided diagnosis system based on artificial intelligence (AI-CADS) in longitudinal and transverse ultrasonic views for differentiating thyroid nodules (TN) was different, which was higher in the transverse section. It was more dependent on the section for the AI-CADS diagnosis of suspected malignant TNs.

Comparison of S-Detect and thyroid imaging reporting and data system classifications in the diagnosis of cytologically indeterminate thyroid nodules.

Purpose: The aim of this study was to investigate the value of S-Detect for predicting the malignant risk of cytologically indeterminate thyroid nodules (CITNs). Methods: The preoperative prediction of 159 CITNs (Bethesda III, IV and V) were performed using S-Detect, Thyroid Imaging Reporting and Data System of American College of Radiology (ACR TI-RADS) and Chinese TI-RADS (C-TIRADS). First, Linear-by-Linear Association test and chi-square test were used to analyze the malignant risk of CITNs. McNemar's test and receiver operating characteristic curve were used to compare the diagnostic efficacy of S-Detect and the two TI-RADS classifications for CITNs. In addition, the McNemar's test was used to compare the diagnostic accuracy of the above three methods for different pathological types of nodules. Results: The maximum diameter of the benign nodules was significantly larger than that of malignant nodules [0.88(0.57-1.42) vs 0.57(0.46-0.81), P=0.002]. The risk of malignant CITNs in Bethesda system and the two TI-RADS classifications increased with grade (all P for trend<0.001). In all the enrolled CITNs, the diagnostic results of S-Detect were significantly different from those of ACR TI-RADS and C-TIRADS, respectively (P=0.021 and P=0.007). The sensitivity and accuracy of S-Detect [95.9%(90.1%-98.5%) and 88.1%(81.7%-92.5%)] were higher than those of ACR TI-RADS [87.6%(80.1%-92.7%) and 81.8%(74.7%-87.3%)] (P=0.006 and P=0.021) and C-TIRADS [84.3%(76.3%-90.0%) and 78.6%(71.3%-84.5%)] (P=0.001 and P=0.001). Moreover, the negative predictive value and the area under curve value of S-Detect [82.8% (63.5%-93.5%) and 0.795%(0.724%-0.855%)] was higher than that of C-TIRADS [54.8%(38.8%-69.8%) and 0.724%(0.648%-0.792%] (P=0.024 and P=0.035). However, the specificity and positive predictive value of S-Detect were similar to those of ACR TI-RADS (P=1.000 and P=0.154) and C-TIRADS (P=1.000 and P=0.072). There was no significant difference in all the evaluated indicators between ACR TI-RADS and C-TIRADS (all P>0.05). The diagnostic accuracy of S-Detect (97.4%) for papillary thyroid carcinoma (PTC) was higher than that of ACR TI-RADS (90.4%) and C-TIRADS (87.8%) (P=0.021 and P=0.003). Conclusion: The diagnostic performance of S-Detect in differentiating CITNs was similar to ACR TI-RADS and superior to C-TIRADS, especially for PTC.

Preoperative Value of Contrast-Enhanced Ultrasound in Totally Laparoscopic Associating Liver Partition and Portal Vein Ligation for Staged Hepatectomy for Liver Tumors: A Preliminary Study.

ABSTRACT: The clinical data of 15 cases that planned to receive totally laparoscopic associating liver partition and portal vein ligation for staged hepatectomy were retrospectively collected. Before the stage 1 operation, the size and number of the tumors in future liver remnant (FLR) and the presence of cancer embolus in the portal vein were assessed using contrast-enhanced ultrasound (CEUS) and contrast-enhanced computed tomography (CECT). Before the stage 2 operation, CEUS was performed to assess the presence of traffic blood flow between the diseased liver and FLR after round-the-liver ligation. Before the stage 1 operation, 5 cases with tumors in FLR were found by CEUS and 6 cases were found by CECT ( P > 0.05). Similarly, CEUS found 5 cases with cancer thrombus in portal vein, and CECT found 7 cases ( P = 0.500). The consistency between the 2 modalities was good (κ = 0.857, P < 0.05, κ = 0.727, P < 0.05, respectively). Before the stage 2 operation, CEUS confirmed that there were 7 cases without traffic blood flow between the diseased liver and FLR, and 3 cases with residual traffic blood flow. The daily growth rate of FLR in the group without traffic blood flow (mean rank = 7.00) was higher than that in the group with traffic blood flow (2.00) significantly ( P < 0.05). Contrast-enhanced ultrasound is a promising application in the preoperative evaluation of totally laparoscopic associating liver partition and portal vein ligation for staged hepatectomy.

Molecular Visual Sensing, Boolean Logic Computing, and Data Security Using a Droplet-Based Superwetting Paradigm.

Inspired by information processing and logic operations of life, many artificial biochemical systems have been designed for applications in molecular information processing. However, encoding the binary synergism between matter, energy, and information in a superwetting system remains challenging. Herein, a superwetting paradigm was proposed for multifunctional applications including molecular visual sensing and data security on a superhydrophobic surface. A Triton X-100-encapsulated gelatin (TeG) hydrogel was prepared and selectively decomposed by trypsin, releasing the surfactant to decrease the surface tension of a droplet. Integrating the droplet with the superhydrophobic surface, the superwetting behavior was utilized for visual detection and information encoding. Interestingly, the proposed TeG hydrogel can function as an artificial gelneuron for molecular-level logic computing, where the combination of matters (superhydrophobic surface, trypsin, and leupeptin) acts as inputs to interact with energy (liquid surface tension and solid surface energy) and information (binary character), resulting in superwettability transitions (droplet surface tension, contact angle, rolling angle, and bounce) as outputs. Impressively, the TeG gelneuron can be further developed as molecular-level double cryptographic steganography to encode, encrypt, and hide specific information (including the maze escape route and content of the classical literature) due to its programmability, stimuli responsive ability, and droplet concealment. This study will encourage the development of advanced molecular paradigms and their applications, such as superwetting visual sensing, molecular computing, interaction, and data security.

Label-Free Resonance Rayleigh Scattering Amplification for Lipopolysaccharide Detection and Logical Circuit by CRISPR/Cas12a-Driven Guanine Nanowire Assisted Non-Cross-Linking Hybridization Chain Reaction.

Although the CRISPR/Cas system has pioneered a new generation of analytical techniques, there remain many challenges in developing a label-free, accurate, and reliable CRISPR/Cas-based assay for reporting the levels of low abundance biomolecules in complex biological samples. Here, we reported a novel CRISPR-derived resonance Rayleigh scattering (RRS) amplification strategy and logical circuit based on a guanine nanowire (G-wire) assisted non-cross-linking hybridization chain reaction (GWancHCR) for label-free detection of lipopolysaccharide (LPS). In the presence of a target, the protospacer-adjacent motif-inserted aptamer is rationally designed to specifically combine with LPS rather than Cas12a, suppressing the trans-cleavage activity of CRISPR/Cas12a and retaining the reporter probes to trigger non-cross-linking aggregation. Owing to the automatic hybridization chain reaction (HCR), in the presence of Mg2+, the released G-quadruplex sequence aggregated to assemble the G-wire superstructure through non-cross-linking. As a result, a dramatically amplified RRS intensity is observed, allowing for reporting LPS levels in a low detection limit of 0.17 pg/mL and a wide linear range among 1.0-100.0 ng/mL. Moreover, this reaction event is capable of programming to perform classical Boolean logic tree analysis, including basic logic computing and complex integrated logic circuits. This study comprehensively analyzed with respect to information flow, matter (molecular events), and energy (RRS), revealing the potential promise in designing of molecular-level "Internet of Things", intelligent computing, and sensing systems.

Feeding Alginate-Coated Liquid Metal Nanodroplets to Silkworms for Highly Stretchable Silk Fibers.

In this study, we fed the larval of Bombyx mori silkworms with nanodroplets of liquid metal (LM) coated with microgels of marine polysaccharides to obtain stretchable silk. Alginate-coated liquid metal nanodroplets (LM@NaAlg) were prepared with significant chemical stability and biocompatibility. This study demonstrates how the fed LM@NaAlg acts on the as-spun silk fiber. We also conducted a series of characterizations and steered molecular dynamics simulations, which showed that the LM@NaAlg additions impede the conformation transition of silk fibroins from the random coil and α-helix to the ß-sheet by the formation of hydrogen bonds between LM@NaAlg and the silk fibroins, thus enhancing the elongation at the breakpoints in addition to the tensile properties. The intrinsically highly stretchable silk showed outstanding mechanical properties compared with regular silk due to its 814 MPa breaking strength and a breaking elongation of up to 70%-the highest reported performance so far. We expect that the proposed method can expand the fabrication of multi-functional silks.

Neuroligin 3 from common cutworm enhances the GABA-induced current of recombinant SlRDL1 channel.

BACKGROUND: Neuroligin (NLG) protein is a nerve cell adhesion molecule and plays a key role in the precision apposition of presynaptic domains on inhibitory and excitatory synapses. Existing studies mainly focused on the function of NLG3 against the excitatory channel. However, the interaction between insect NLG3 and ionotropic GABA receptor, which is the main inhibitory channel, remains unclear. In this study, the Nlg3 of common cutworm (CCW), Spodoptera litura Fabricius, one important agricultural Lepidopteron, is selected to explore its function in the inhibitory channel. RESULTS: The SlNlg3 was obtained and the SlNLG3 contains the characteristic features including transmembrane domain, PDZ-binding motif and type-B carboxylesterases signature 2 motif. The SlNlg3 messenger RNA (mRNA) was most abundant in midgut, and exhibited multiple expression patterns in different developmental stages and tissues or body parts. Compared with the single injection of SlRDL1, the median effective concentration value of GABA in activating currents was smaller in Xenopus laevis oocytes co-injected with SlRDL1 and SlNlg3. In addition, SlNlg3 could enhance the GABA-induced current of homomeric SlRDL1 channel from -391.86 ± 15.41 to -2152.51 ± 30.09 nA. DsSlNlg3 depressed the expression level of SlNlg3 mRNA more than 64.29% at 6 h. After exposure to median lethal dose of fluralaner, the mortality of CCW injected with dsSlNlg3 was significantly decreased by 13.34% and 30.00% at 24 and 48 h, respectively, compared to injection of dsEGFP. CONCLUSION: NLG3 should have physiological function on ionotropic GABA receptor in vitro, which provided a favorable foundation for further research on the physiological function of Nlg gene in Lepidopteron. © 2021 Society of Chemical Industry.

Protein-DNA Binding Residue Prediction via Bagging Strategy and Sequence-Based Cube-Format Feature.

Protein-DNA interactions play an important role in diverse biological processes. Accurately identifying protein-DNA binding residues is a critical but challenging task for protein function annotations and drug design. Although wet-lab experimental methods are the most accurate way to identify protein-DNA binding residues, they are time consuming and labor intensive. There is an urgent need to develop computational methods to rapidly and accurately predict protein-DNA binding residues. In this study, we propose a novel sequence-based method, named PredDBR, for predicting DNA-binding residues. In PredDBR, for each query protein, its position-specific frequency matrix (PSFM), predicted secondary structure (PSS), and predicted probabilities of ligand-binding residues (PPLBR) are first generated as three feature sources. Secondly, for each feature source, the sliding window technique is employed to extract the matrix-format feature of each residue. Then, we design two strategies, i.e., square root (SR) and average (AVE), to separately transform PSFM-based and two predicted feature source-based, i.e., PSS-based and PPLBR-based, matrix-format features of each residue into three corresponding cube-format features. Finally, after serially combining the three cube-format features, the ensemble classifier is generated via applying bagging strategy to multiple base classifiers built by the framework of 2D convolutional neural network. The computational experimental results demonstrate that the proposed PredDBR achieves an average overall accuracy of 93.7% and a Mathew's correlation coefficient of 0.405 on two independent validation datasets and outperforms several state-of-the-art sequenced-based protein-DNA binding residue predictors. The PredDBR web-server is available at https://jun-csbio.github.io/PredDBR/.

Research progress regarding programmed cell death 1/programmed cell death ligand 1 inhibitors combined with targeted therapy for treating hepatocellular carcinoma.

In recent years, a number of targeted therapeutic agents have achieved success in phase III trials in patients with advanced hepatocellular carcinoma (HCC), including sorafenib, lenvatinib, and regorafenib. Immunotherapy is considered to be an effective treatment for advanced HCC. Immune checkpoint inhibitors targeting programmed cell death 1 (PD-1)/programmed cell death ligand 1 (PD-L1) are important antitumor immunotherapy agents that represent breakthroughs in the treatment of advanced HCC. However, treating advanced HCC is still a great challenge, and the need for new treatments remains urgent. This review briefly summarizes the research progress in the use of PD-1/PD-L1 inhibitors combined with targeted therapy for treating HCC.

pH-Responsive DNA Motif: From Rational Design to Analytical Applications.

pH-responsive DNA motifs have attracted substantial attention attributed to their high designability and versatility of DNA chemistry. Such DNA motifs typically exploit DNA secondary structures that exhibit pH response properties because of the presence of specific protonation sites. In this review, we briefly summarized second structure-based pH-responsive DNA motifs, including triplex DNA, i-motif, and A+-C mismatch base pair-based DNA devices. Finally, the challenges and prospects of pH-responsive DNA motifs are also discussed.

Accurate prediction of protein-ATP binding residues using position-specific frequency matrix.

Knowledge of protein-ATP interaction can help for protein functional annotation and drug discovery. Accurately identifying protein-ATP binding residues is an important but challenging task to gain the knowledge of protein-ATP interactions, especially for the case where only protein sequence information is given. In this study, we propose a novel method, named DeepATPseq, to predict protein-ATP binding residues without using any information about protein three-dimension structure or sequence-derived structural information. In DeepATPseq, the HHBlits-generated position-specific frequency matrix (PSFM) profile is first employed to extract the feature information of each residue. Then, for each residue, the PSFM-based feature is fed into two prediction models, which are generated by the algorithms of deep convolutional neural network (DCNN) and support vector machine (SVM) separately. The final ATP-binding probability of the corresponding residue is calculated by the weighted sum of the outputted values of DCNN-based and SVM-based models. Experimental results on the independent validation data set demonstrate that DeepATPseq could achieve an accuracy of 77.71%, covering 57.42% of all ATP-binding residues, while achieving a Matthew's correlation coefficient value (0.655) that is significantly higher than that of existing sequence-based methods and comparable to that of the state-of-the-art structure-based predictors. Detailed data analysis show that the major advantage of DeepATPseq lies at the combination utilization of DCNN and SVM that helps dig out more discriminative information from the PSFM profiles. The online server and standalone package of DeepATPseq are freely available at: https://jun-csbio.github.io/DeepATPseq/for academic use.

MicroRNAs: Multifaceted Regulators of Colorectal Cancer Metastasis and Clinical Applications.

Colorectal cancer (CRC) is the third-commonest malignant cancer, and its metastasis is the major reason for cancer-related death. The process of metastasis is highly coordinated and involves a complex cascade of multiple steps. In recent years, miRNAs, as highly conserved, endogenous, noncoding, single-stranded RNA, has been confirmed to be involved in the development of various cancers. Considering that miRNA is also involved in a series of biological behaviors, regulating CRC occurrence and development, we review and summarize the role of miRNAs and related signaling pathways in several CRC-metastasis stages, including invasion and migration, mobility, metabolism, epithelial-mesenchymal transition, tumor-microenvironment communication, angiogenesis, anoikis, premetastatic-niche formation, and cancer stemness. In addition, we review the application of miRNAs as diagnostic CRC markers and in clinical treatment resistance. This review can contribute to understanding of the mechanism of miRNAs in CRC progression and provide a theoretical basis for clinical CRC treatment.

LNCRNA CDKN2B-AS1 regulates mesangial cell proliferation and extracellular matrix accumulation via miR-424-5p/HMGA2 axis.

BACKGROUND: Previous study has demonstrated that long noncoding RNA cyclin-dependent kinase inhibitor 2B antisense RNA 1 (CDKN2B-AS1) was abnormally expressed in diabetic nephropathy (DN). However, the underlying mechanism that allows CDKN2B-AS1 in the progression of DN remains to be further elucidated. METHODS: Peripheral blood cells of 24 diabetes patients with DN and 20 without DN were collected. Human glomerular mesangial cells (HGMC) were cultured in high glucose or low glucose medium. The expression levels of CDKN2B-AS1, microRNA (miR)-424-5p and high mobility group AT hook 2 (HMGA2) were detected by quantitative real-time polymerase chain reaction or western blot. The target association between miR-424-5p and CDKN2B-AS1 or HMGA2 was confirmed by dual-luciferase reporter and RNA immunoprecipitation assays. Cell proliferation, extracellular matrix (ECM) accumulation and phosphatidylinositol 3-kinase (PI3K)/protein kinase B (AKT) signaling were investigated by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-tetrazolium bromide (MTT) and western blot, respectively. RESULTS: CDKN2B-AS1 expression was up-regulated and miR-424-5p level was down-regulated in peripheral blood of DN patients and high glucose-treated HGMC cells. CDKN2B-AS1 was validated as a sponge of miR-424-5p. Silence of CDKN2B-AS1 repressed proliferation and ECM accumulation by increasing miR-424-5p. HMGA2 was a target of miR-424-5p and miR-424-5p overexpression inhibited proliferation, ECM accumulation and PI3K/AKT pathway by targeting HMGA2. Moreover, knockdown of CDKN2B-AS1 inhibited HMGA2 expression and PI3K/AKT pathway by increasing miR-424-5p. CONCLUSION: Knockdown of CDKN2B-AS1 suppressed proliferation, ECM accumulation and PI3K/AKT signaling by increasing miR-424-5p and decreasing HMGA2 in high glucose-treated HMGC cells.

Constituents from the Leaves of Tetraena mongolica and Their Protective Activity in HEK 293t Cells Damaged by CdCl2.

Tetraena mongolica Maxim, a relict originating from the Tertiary Period, is an endemic species of Zygophyllaceae in China. Three new monoterpenoids (1-3), two new phenols (4, 5) with unusual O-sulfoglucosyl groups, a new flavonoid (6), and nine known compounds were isolated from the leaves of T. mongolica. The structures of these compounds were determined by interpretation of NMR, MS, and ECD data. Some of the isolated compounds showed protective effects on HEK 293t cells damaged by CdCl2, with IC50 values being 55.7 and 80.3 µM for compounds 7 and 8, respectively, at the time point of 48 h after treatment.

[Effect of electroacupuncture at "Jiaji" (EX-B 2) points combined with nerve mobilization on motor function and mRNA and protein expression of RhoA in rabbits with sciatic nerve injury].

OBJECTIVE: To observe the effects of electroacupuncture (EA) at "Jiaji" (EX-B 2) points combined with nerve mobilization on protein and mRNA expression of RhoA in rabbits with sciatic nerve injury, and to provide theoretical basis for the treatment of peripheral nerve injury by EA at "Jiaji" (EX-B 2) points combined with nerve mobilization. METHODS: A total of 180 New Zealand rabbits were randomly divided into a normal control group, a model control group, a nerve mobilization group, an EA group, an EA plus nerve mobilization group, 36 rabbits in each group. Each group was further divided into a 1-week subgroup, 2-week subgroup and 4-week subgroup, 12 rabbits in each subgroup. The sciatic nerve injury model was made by clamping method. The rabbits in the normal control group did not receive any intervention. The rabbits in the model control group was normally fed after operation. The rabbits in the nerve mobilization group were treated with nerve mobilization; the manipulation lasted for 1 s and relaxed for 5 s, 10 times per day, 6 days per week. The rabbits in the EA group were treated with EA at "Jiaji" (EX-B 2) points (L4-L6), once a day, 30 min each time, 6 times per week. The rabbits in the EA plus nerve mobilization group were treated with EA at "Jiaji" (EX-B 2) points, followed by nerve mobilization. The function of sciatic nerve on the injured side was evaluated by toe tension reflex and modified Tarlov score; the tissues of corresponding segments of spinal cord L4-L6 and sciatic nerve were taken; the expression of RhoA gene was detected by real-time PCR and the expression of RhoA protein was detected by Western Blot. RESULTS: ① Toe tension reflex and modified Tarlov score: at 1, 2 and 4 weeks, the scores in the model control group were lower than those in the normal control group (all P<0.01). The scores in the subgroup of nerve mobilization group, EA group and EA plus nerve mobilization group were higher than those in the model control group (all P<0.01), and the scores in the subgroup of EA plus nerve mobilization group were higher than those in the nerve mobilization group and the EA group (all P<0.01); the recovery was the best at 4 weeks. ② The mRNA and protein expression of RhoA: in segment of spinal cord, at 1, 2 and 4 weeks, the expression in the model control group was higher than that in the normal control group (all P<0.01). The expression in the subgroup of nerve mobilization group, EA group and EA plus nerve mobilization group was lower than that in the model control group (all P<0.01), and the expression in the subgroup of EA plus nerve mobilization group was lower than that in the nerve mobilization group and the EA group (all P<0.01); at 1 week and 4 weeks, the expression in the nerve mobilization group was lower than that in the EA group (all P<0.01); at 2 weeks, the expression in the nerve mobilization group was higher than that in the EA group (all P<0.01). In the sciatic nerve, at 1, 2 and 4 weeks, the expression in the model control group was higher than that in the normal control group (all P<0.01). The expression in the subgroup of nerve mobilization group, EA group and EA plus nerve mobilization group was lower than that in the model control group (all P<0.01); at 2 weeks and 4 weeks, the expression in the EA plus nerve mobilization group was lower than that in the nerve mobilization group and EA group (all P<0.01); at 1 week, the expression in the nerve mobilization group was lower than that in the EA group and EA plus nerve mobilization group (all P<0.01), but the differences between the EA group and the EA plus nerve mobilization group were not significant (P>0.05); at 2 weeks, the expression in the nerve mobilization group was higher than that in the EA group (all P<0.01); at 4 weeks, the expression in the nerve mobilization group was lower than that in the EA group (all P<0.01). CONCLUSION: The nerve mobilization and EA at "Jiaji" (EX-B 2) points could both promote the repair of injured sciatic nerve, which may be related to the down-regulation of RhoA expression, and the combination of the two methods has better effects.