Publications by authors named "Xiaoli Li"

789 Publications

The application and progression of CRISPR/Cas9 technology in ophthalmological diseases.

Eye (Lond) 2022 Aug 1. Epub 2022 Aug 1.

Henan Eye Hospital, Henan Eye Institution, Henan Provincial People's Hospital, Zhengzhou University People's Hospital, Zhengzhou, 450003, Henan, China.

The clustered regularly interspaced short palindromic repeats (CRISPR)/CRISPR-associated nuclease (Cas) system is an adaptive immune defence system that has gradually evolved in bacteria and archaea to combat invading viruses and exogenous DNA. Advances in technology have enabled researchers to enhance their understanding of the immune process in vivo and its potential for use in genome editing. Thus far, applications of CRISPR/Cas9 genome editing technology in ophthalmology have included gene therapy for corneal dystrophy, glaucoma, congenital cataract, Leber's congenital amaurosis, retinitis pigmentosa, Usher syndrome, fundus neovascular disease, proliferative vitreoretinopathy, retinoblastoma and other eye diseases. Additionally, the combination of CRISPR/Cas9 genome editing technology with adeno-associated virus vector and inducible pluripotent stem cells provides further therapeutic avenues for the treatment of eye diseases. Nonetheless, many challenges remain in the development of clinically feasible retinal genome editing therapy. This review discusses the development, as well as mechanism of CRISPR/Cas9 and its applications and challenges in gene therapy for eye diseases.
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http://dx.doi.org/10.1038/s41433-022-02169-1DOI Listing
August 2022

Discoidin domain receptor 1(DDR1) promote intestinal barrier disruption in Ulcerative Colitis through tight junction proteins degradation and epithelium apoptosis.

Pharmacol Res 2022 Jul 26;183:106368. Epub 2022 Jul 26.

Department of Gastroenterology, The Second Clinical Medical College of Lanzhou University, LanZhou University Second Hospital, Lanzhou, China; Key Laboratory of Digestive Diseases, LanZhou University Second Hospital, Lanzhou, China. Electronic address:

Background And Aims: Discoidin domain receptor 1 (DDR1) encodes a receptor tyrosine kinase involved in multiple physiological and pathological processes. DDR1 is expressed in the intestinal epithelium, but its role in Ulcerative Colitis (UC) is poorly understand. This study aimed to identify the function of DDR1 in maintaining the homeostasis of UC.

Methods: The DDR1 expression level in non-inflamed and inflamed colon samples from IBD patients were assessed. DDR1 knock-out (DDR1) and wild-type (WT) mice were administered dextran sulfate sodium (DSS) to induce colitis and assessed based on colitis symptoms. In addition, intestinal epithelial barrier injury was induced by TNF-α and IFN-γ incubation to cell monolayers transfected with PCDH-DDR1 or pLKO.1-sh-DDR1-1 plasmids. The effect of DDR1 in regulating barrier integrity, tight junctions (TJ) protein status, and cell apoptosis was investigated in vivo and in vitro. Furthermore, the activation of the NF-κB p65-MLCK-p-MLC2 pathway was also investigated.

Results: Decreased DDR1 expression levels were observed at the inflamed sites compared with the non-inflamed. DDR1 mice had alleviated intestinal mucosal barrier injuries, upregulated TJ proteins, decreased epithelium apoptosis from DSS-induced colitis, and reduced proinflammatory cytokines production in the colon. These findings were further confirmed in vitro. DDR1 over-expression aggravated the TNF-α/IFN-γ-induced TJ disruption, while DDR1 shRNA prevented TJ damage even in the presence of JSH-23. DDR1 dependently destroyed the intestinal barrier via the NF-κB p65-MLCK-p-MLC2 pathway.

Conclusion: Our findings revealed that DDR1 regulated the intestinal barrier in colitis by modulating TJ proteins expression and epithelium apoptosis, making it a potential target of UC.
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http://dx.doi.org/10.1016/j.phrs.2022.106368DOI Listing
July 2022

Riemannian Manifold-Based Feature Space and Corresponding Image Clustering Algorithms.

IEEE Trans Neural Netw Learn Syst 2022 Jul 22;PP. Epub 2022 Jul 22.

Image feature representation is a key factor influencing the accuracy of clustering. Traditional point-based feature spaces represent spectral features of an image independently and introduce spatial relationships of pixels in the image domain to enhance the contextual information expression ability. Mapping-based feature spaces aim to preserve the structure information, but the complex computation and the unexplainability of image features have a great impact on their applications. To this end, we propose an explicit feature space called Riemannian manifold feature space (RMFS) to present the contextual information in a unified way. First, the Gaussian probability distribution function (pdf) is introduced to characterize the features of a pixel in its neighborhood system in the image domain. Then, the feature-related pdfs are mapped to a Riemannian manifold, which constructs the proposed RMFS. In RMFS, a point can express the complex contextual information of corresponding pixel in the image domain, and pixels representing the same object are linearly distributed. This gives us a chance to convert nonlinear image segmentation problems to linear computation. To verify the superiority of the expression ability of the proposed RMFS, a linear clustering algorithm and a fuzzy linear clustering algorithm are proposed. Experimental results show that the proposed RMFS-based algorithms outperform their counterparts in the spectral feature space and the RMFS-based ones without the linear distribution characteristics. This indicates that the RMFS can better express features of an image than spectral feature space, and the expressed features can be easily used to construct linear segmentation models.
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http://dx.doi.org/10.1109/TNNLS.2022.3190836DOI Listing
July 2022

Munronoid I Ameliorates DSS-Induced Mouse Colitis by Inhibiting NLRP3 Inflammasome Activation and Pyroptosis Modulation of NLRP3.

Front Immunol 2022 5;13:853194. Epub 2022 Jul 5.

Marshall Laboratory of Biomedical Engineering, Department of Immunology, Shenzhen University School of Medicine, Shenzhen, China.

Inflammatory bowel diseases (IBDs) are increasingly common diseases characterized by chronic and relapsing inflammation of the gastrointestinal tract. NLRP3 might be a crucial regulator of the homeostatic balance of the intestine, but its upregulation leads to pyroptosis. Munronoid I is extracted and purified from , which has shown an anti-inflammatory effect, but the efficacy of Munronoid I in IBD remains unproven. In this study, we attempted to determine the effect of Munronoid I on NLRP3 to regulate the inflammasome activation and pyroptosis in IBD. Our data demonstrated that Munronoid I treatment attenuated DSS-induced body weight loss, pathological injury of the colon, the production of IL-1β and IL-18, and the expression of pyroptosis-associated proteins in colon tissue in mice. Moreover, Munronoid I inhibited LPS/ATP-induced pyroptosis in mouse peritoneal macrophages, MODE-K cells, and DSS-induced pyroptosis in mouse colonic epithelial cells, and decreased the release of inflammatory cytokines IL-1β and IL-18 in mouse peritoneal macrophages. Mechanically, Munronoid I could suppress the NLRP3 inflammasome activation and pyroptosis by promoting the K48-linked ubiquitination and NLRP3 degradation. It is suggested that Munronoid I might be a potential therapeutic candidate for IBD.
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http://dx.doi.org/10.3389/fimmu.2022.853194DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9296101PMC
July 2022

A Multimodal Approach for Identifying Autism Spectrum Disorders in Children.

IEEE Trans Neural Syst Rehabil Eng 2022 22;30:2003-2011. Epub 2022 Jul 22.

Identification of autism spectrum disorder (ASD) in children is challenging due to the complexity and heterogeneity of ASD. Currently, most existing methods mainly rely on a single modality with limited information and often cannot achieve satisfactory performance. To address this issue, this paper investigates from internal neurophysiological and external behavior perspectives simultaneously and proposes a new multimodal diagnosis framework for identifying ASD in children with fusion of electroencephalogram (EEG) and eye-tracking (ET) data. Specifically, we designed a two-step multimodal feature learning and fusion model based on a typical deep learning algorithm, stacked denoising autoencoder (SDAE). In the first step, two SDAE models are designed for feature learning for EEG and ET modality, respectively. Then, a third SDAE model in the second step is designed to perform multimodal fusion with learned EEG and ET features in a concatenated way. Our designed multimodal identification model can automatically capture correlations and complementarity from behavior modality and neurophysiological modality in a latent feature space, and generate informative feature representations with better discriminability and generalization for enhanced identification performance. We collected a multimodal dataset containing 40 ASD children and 50 typically developing (TD) children to evaluate our proposed method. Experimental results showed that our proposed method achieved superior performance compared with two unimodal methods and a simple feature-level fusion method, which has promising potential to provide an objective and accurate diagnosis to assist clinicians.
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http://dx.doi.org/10.1109/TNSRE.2022.3192431DOI Listing
July 2022

Chemotherapy Combined With Immunotherapy as a First-Line Treatment Brings Benefits to Patients With Lung Squamous Cell Carcinoma but Different Risks of Adverse Reactions: A Systematic Review and Meta-Analysis.

Front Pharmacol 2022 1;13:940567. Epub 2022 Jul 1.

Department of Anesthesiology, Zoucheng People's Hospital, Jining, China.

To explore the efficacy and safety of chemotherapy combined with immunotherapy as the first-line treatment of advanced or metastatic squamous NSCLC. Two researchers independently searched PubMed, the Cochrane Library, EMBASE, CNKI, Wanfang Data, and other databases by using a computer, collected the clinical trials or randomized controlled trials published by April 2022 about immunotherapy combined with chemotherapy as the first-line treatment of advanced or metastatic squamous NSCLC, screened the literature, and extracted the data according to the nanodischarge criteria. We used Revman5.4 for statistical analysis of the included studies, and publication bias was analyzed with Egger's test in Stata12. A total of seven clinical trials were included, including 1,510 cases in the chemotherapy combined with the immunotherapy group and 1,519 cases in the chemotherapy group. In terms of effectiveness, compared with the chemotherapy group, chemotherapy combined with immunotherapy for advanced or metastatic squamous NSCLC had longer overall survival (HR = 1.59, 95% CI: 1.46-1.72, < 0.00001) and progression-free survival (HR = 1.84, 95% CI: 1.66-2.03, < 0.00001). In terms of safety, the chemotherapy combined with immunotherapy group has a higher risk of adverse reactions at any level and above three levels of hematotoxicity, gastrointestinal abnormalities, and liver dysfunction than the chemotherapy group. Egger's test has minor publication bias. Chemotherapy combined with immunotherapy is effective as the first-line treatment for advanced or metastatic squamous NSCLC, but the risk of adverse reactions is relatively high. If there are adverse reactions in clinical application, it should be treated in time.
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http://dx.doi.org/10.3389/fphar.2022.940567DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9283920PMC
July 2022

T-17, a novel cyclin-dependent kinases/histone deacetylases dual inhibitor, induces cancer cells death through cell cycle arrest and apoptosis.

Drug Dev Res 2022 Jul 17. Epub 2022 Jul 17.

Department of Medicinal Chemistry, College of Pharmacy, Chongqing Medical University, Chongqing, China.

Combination of cyclin-dependent kinases (CDKs) and histone deacetylases (HDACs) inhibitors may have statistical synergy in suppressing cancer cell proliferation. Herein, a novel CDKs/HDACs dual inhibitor T-17 was rationally designed, synthesized, and evaluated. Our results demonstrated that T-17 concurrently exhibited potent and balanced inhibitory activity against CDKs (IC  = 18.0 nM) and HDACs (IC  = 6.6 nM) and also displayed good cell viability inhibitory effect on four cancer cell lines. Meanwhile, T-17 blocked the MDA-MB-231 and A549 cell cycle at G1 phase and S phase, respectively. In addition, T-17 induced MDA-MB-231 cells apoptosis and inhibited the HDACs and CDKs mediated signaling pathways. Finally, we also found that T-17 had good antitumor activity in vivo. In summary, these results indicated that T-17 would be a promising lead compound which deserves further research.
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http://dx.doi.org/10.1002/ddr.21977DOI Listing
July 2022

Progranulin, a moderator of estrogen/estrogen receptor α binding, regulates bone homeostasis through PERK/p-eIF2 signaling pathway.

J Mol Med (Berl) 2022 Aug 15;100(8):1191-1207. Epub 2022 Jul 15.

Department of Cell Biology and Genetics, Core Facility of Development Biology, Chongqing Medical University, Chongqing, 400016, China.

Under normal conditions, the human body employs the synergistic action of osteoblasts and osteoclasts to maintain a dynamic balance between bone formation and resorption. Bone homeostasis plays a very important role in the process of bone formation. Various bone diseases can occur if bone homeostasis is disrupted. In this study, the serum estrogen levels were significantly increased in the granulin (GRN)-deficient mice and PGRN regulates the binding of estrogen and estrogen receptor α (ERα) and then affects estrogen's ability to regulate bone formation and resorption. In addition, this study also explored the role that PGRN plays in regulating bone homeostasis by affecting the binding of estrogen and estrogen receptors through the protein kinase R-like endoplasmic reticulum kinase/phosphorylation of the eukaryotic initiation factor 2 signaling pathway. In summary, we confirmed the important role of PGRN in regulating the estrogen (E2)/ERα signal in maintaining bone homeostasis. Our findings may provide a new strategy for the treatment of osteoporosis and maintaining bone homeostasis. KEY MESSAGES: PGRN is a molecular regulator of the binding of E2 and ERα signal in maintaining bone homeostasis. PGRN plays in regulating bone homeostasis through the PERK/p-eIF2α signaling pathway. The best therapeutic effect of PGRN in osteoporosis is associated with different concentration of E2.
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http://dx.doi.org/10.1007/s00109-022-02233-zDOI Listing
August 2022

Cell cycle arrest explains the observed bulk 3D genomic alterations in response to long-term heat shock in K562 cells.

Genome Res 2022 Jul 14;32(7):1285-1297. Epub 2022 Jul 14.

Beijing Institute of Genomics, Chinese Academy of Sciences, and China National Center for Bioinformation, Chaoyang District, Beijing 100101, China.

Heat shock is a common environmental stress, although the response of the nucleus to it remains controversial in mammalian cells. Acute reaction and chronic adaptation to environmental stress may have distinct internal rewiring in the gene regulation networks. However, this difference remains largely unexplored. Here, we report that chromatin conformation and chromatin accessibility respond differently in short- and long-term heat shock in human K562 cells. We found that chromatin conformation in K562 cells was largely stable in response to short-term heat shock, whereas it showed clear and characteristic changes after long-term heat treatment with little alteration in chromatin accessibility during the whole process. We further show in silico and experimental evidence strongly suggesting that changes in chromatin conformation may largely stem from an accumulation of cells in the M stage of the cell cycle in response to heat shock. Our results represent a paradigm shift away from the controversial view of chromatin response to heat shock and emphasize the necessity of cell cycle analysis when interpreting bulk Hi-C data.
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http://dx.doi.org/10.1101/gr.276554.122DOI Listing
July 2022

Comparison of Haploidentical Hematopoietic Stem Cell Transplant With or Without Unrelated Cord Blood Infusion in Severe Aplastic Anemia: Outcomes of a Multicenter Study.

Front Immunol 2022 23;13:912917. Epub 2022 Jun 23.

The First Affiliated Hospital of Soochow University, Jiangsu Institute of Hematology, Key Laboratory of Thrombosis and Hemostasis of Ministry of Health, Collaborative Innovation Center of Hematology, Suzhou, China.

The purpose of this study in severe aplastic anemia (SAA) patients was to compare the feasibility and efficacy of haploidentical hematological stem cell transplantation combined with a single unrelated cord blood (UCB) infusion (Haplo-cord-HSCT) or haplo-identical HSCT (Haplo-HSCT) alone. The five-year graft-versus-host disease (GVHD)-free or failure-free survival (GFFS) was similar between the two groups (72.4 ± 3.4% vs. 65.4 ± 5.2%, P = 0.178); however, the five-year overall survival (OS) was more favorable in the Haplo-cord-HSCT group than that in the Haplo-HSCT group (84.0 ± 2.8% vs. 72.6 ± 4.9%, P = 0.022), as was transplantation-related mortality (16.4% vs. 27.4%, P = 0.039). Multivariate analysis showed that Haplo-cord HSCT was the only independent determinant of increased OS (P = 0.013). Explorative subgroup analysis showed that only an Human leukocyte antigen-A (HLA-A) allele match between UCB and the recipient was a beneficial factor for GFFS in the Haplo-cord-HSCT group (P = 0.011). In the haplo-cord with an HLA-A match (n = 139) or mismatch (n = 32) or Haplo-HSCT groups, a haplo-cord HLA-A allele match was associated with lower I-IV and III-IV acute GVHD. The haplo-cord with an HLA-A match subgroup also had higher five-year OS than the Haplo-HSCT group (85.4 ± 3.0% vs. 72.6 ± 4.9%, P = 0.013), and higher five-year GFFS than the Haplo-cord HLA-A allele mismatch subgroup (76.2 ± 3.6% vs. 56.3 ± 8.8%, P = 0.011). These findings suggest that the coinfusion of a single UCB potentially improves survival of Haplo-HSCT in SAA patients and that an HLA-A allele-matched UCB is the preferred option.
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http://dx.doi.org/10.3389/fimmu.2022.912917DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9259833PMC
June 2022

Special manifestations and treatment of rare cases of snoring with special facial features and hearing loss in children.

J Int Med Res 2022 Jul;50(7):3000605221108085

Department of Otolaryngology and Head and Neck Surgery, Shanghai Children's Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China.

This current case report describes two rare cases of children with both hearing loss and snoring. Case 1, a 17-month-old male patient, and case 2, an 11-year-old male patient, both presented with nasal obstruction, snoring and hearing loss. Physical examinations showed obvious enlargement of the head circumference and special facial features. The two children underwent otolaryngology examinations, endoscopy, hearing tests, laboratory examinations for bone metabolism markers, cranial computed tomography, X-rays and genome-wide exon sequencing. The first case was diagnosed with craniometaphyseal dysplasia, which was relieved after giving a low-calcium diet. The second case was diagnosed with osteopathia striata with cranial sclerosis by gene sequencing. Snoring improved after medication and the speech and quality of life improved with a hearing aid. Paediatric otolaryngological physicians need to have a deeper understanding of congenital diseases involving the bones. Only by genetic testing to determine the pathogenesis can those children be given the correct treatment, which is of great importance for improving their prognosis.
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http://dx.doi.org/10.1177/03000605221108085DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9274808PMC
July 2022

Clinical Characteristics in Patients with Redetected Positive RNA Test After Recovery from Foreign-Imported COVID-19 Cases in Xi'an, China.

Infect Drug Resist 2022 24;15:3295-3307. Epub 2022 Jun 24.

Department of Respiratory, Honghui Hospital, Xi'an Jiaotong University, Xi'an, Shaanxi, 710054, People's Republic of China.

Purpose: At present, it has been found that managing patients with a redetected positive RNA test after recovery from foreign-imported coronavirus disease 2019 (COVID-19) cases in China is challenging. The purpose of the current study was to describe the clinical characteristics of these patients.

Methods: This retrospective cohort study included 137 COVID-19 patients who were discharged from the Xi'an Public Health Center from 28 July 2020 to 31 December 2021. We compared the clinical characteristics between positive retest patients and non-positive retest patients.

Results: 137 COVID-19 patients entered our study, 27 (19.7%) cases of COVID-19 with a redetected positive RNA test by the end of the follow-up period. Fever [(n = 31 (22.6%)], cough [n = 26 (18.9%)] and sore throat [n = 20 (14.5%)] were the most common initial symptoms among the foreign-imported COVID-19 patients, and there were almost no significant differences in initial symptoms between positive retest patients and non-positive retest patients. The positive retest patients had a higher lymphocyte count (p = 0.031) and lymphocyte percentage (p = 0.007) during readmission. There were generally no significant differences in other routine blood test findings, IgG and IgM antibody responses, between positive retest patients and non-positive retest patients, or in positive retest patients over time (before, during, or after positive patient detection). After readmission, positive retest patients displayed fewer symptoms or no obvious disease progression and more sustained remission by CT imaging.

Conclusion: Our findings revealed that the clinical characteristics at the time of initial diagnosis were not closely related to redetected positive RNA tests after recovery from foreign-imported COVID-19 cases. Positive retest patients had virtually no symptoms and displayed no obvious disease progression during readmission. These findings provide important information and clinical evidence for the effective management of foreign-imported COVID-19 patients during their convalescent phase.
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http://dx.doi.org/10.2147/IDR.S371088DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9239575PMC
June 2022

Mechanism of Liver Regeneration During ALPPS.

Front Cell Dev Biol 2022 8;10:916286. Epub 2022 Jun 8.

Department of General Surgery, Xiangya Hospital, Central South University, Changsha, China.

Liver cancer is one of the most lethal malignant tumors in the world, and surgical resection is the main treatment for liver cancer. Liver failure due to insufficient residual liver volume is a fatal complication after hepatectomy. How to effectively increase the residual liver volume after hepatectomy and improve the safety of hepatectomy has always been a problem to be solved in liver surgery. Associating liver partition and portal vein ligation for staged hepatectomy (ALPPS) effectively reduces the occurrence of liver failure due to insufficient residual liver volume after hepatectomy, thereby increasing the probability of radical resection by inducing rapid proliferation of residual liver tissue. However, the molecular mechanism of residual liver tissue regeneration after primary ALPPS (combined liver partition and portal vein ligation) remains unclear. Here, we found that lots of circular RNAs (circRNAs) are upregulated after ALPPS in pig liver cells; then, we identified the orthologous circRNA in humans and pigs to detect their function in liver regeneration. The results showed that loss of circ-0067724 and circ-0016213 could suppress liver cell proliferation. Together, these findings suggest that circ-0067724 and circ-0016213 play an important role in liver cell proliferation, and this may help us to find new strategies to promote liver regeneration.
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http://dx.doi.org/10.3389/fcell.2022.916286DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9213876PMC
June 2022

Machine Learning-Based Model for Prediction of Hemorrhage Transformation in Acute Ischemic Stroke After Alteplase.

Front Neurol 2022 10;13:897903. Epub 2022 Jun 10.

Department of Neurology, ZhongDa Hospital Southeast University (JiangBei) (NanJing DaChang Hospital), Nanjing, China.

Hemorrhage transformation (HT) is the most dreaded complication of intravenous thrombolysis (IVT) in acute ischemic stroke (AIS). The prediction of HT after IVT is important in the treatment decision-making for AIS. We designed and compared different machine learning methods, capable of predicting HT in AIS after IVT. A total of 345 AIS patients who received intravenous alteplase between January 2016 and June 2021 were enrolled in this retrospective study. The demographic characteristics, clinical condition, biochemical data, and neuroimaging variables were included for analysis. HT was confirmed by head computed tomography (CT) or magnetic resonance imaging (MRI) within 48 h after IVT. Based on the neuroimaging results, all of the patients were divided into the non-HT group and the HT group. Then, the variables were applied in logistic regression (LR) and random forest (RF) algorithms to establish HT prediction models. To evaluate the accuracy of the machine learning models, the models were compared to several of the common scales used in clinics, including the multicenter stroke survey (MSS) score, safe implementation of treatments in stroke (SITS) score, and SEDAN score. The performance of these prediction models was evaluated using the receiver operating characteristic (ROC) curve (AUC). Forty-five patients had HT (13.0%) within 48 h after IVT. The ROC curve results showed that the AUCs of HT that were predicted by the RF model, LR model, MSS, SITS, and SEDAN scales after IVT were 0.795 (95% CI, 0.647-0.944), 0.703 (95% CI, 0.515-0.892), 0.657 (95% CI, 0.574-0.741), 0.660 (95% CI, 0.580-0.740) and 0.655 (95% CI, 0.571-0.739), respectively. The RF model performed better than the other models and scales. The top four most influential factors in the RF importance matrix plot were triglyceride, Lpa, the baseline NIHSS, and hemoglobin. The SHapley Additive exPlanation values made the RF prediction model clinically interpretable. In this study, an RF machine learning method was successfully established to predict HT in AIS patients after intravenous alteplase, which the sensitivity was 66.7%, and the specificity was 80.7%.
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http://dx.doi.org/10.3389/fneur.2022.897903DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9226411PMC
June 2022

Self-Supervised Autoregressive Domain Adaptation for Time Series Data.

IEEE Trans Neural Netw Learn Syst 2022 Jun 23;PP. Epub 2022 Jun 23.

Unsupervised domain adaptation (UDA) has successfully addressed the domain shift problem for visual applications. Yet, these approaches may have limited performance for time series data due to the following reasons. First, they mainly rely on the large-scale dataset (i.e., ImageNet) for source pretraining, which is not applicable for time series data. Second, they ignore the temporal dimension on the feature space of the source and target domains during the domain alignment step. Finally, most of the prior UDA methods can only align the global features without considering the fine-grained class distribution of the target domain. To address these limitations, we propose a SeLf-supervised AutoRegressive Domain Adaptation (SLARDA) framework. In particular, we first design a self-supervised (SL) learning module that uses forecasting as an auxiliary task to improve the transferability of source features. Second, we propose a novel autoregressive domain adaptation technique that incorporates temporal dependence of both source and target features during domain alignment. Finally, we develop an ensemble teacher model to align class-wise distribution in the target domain via a confident pseudo labeling approach. Extensive experiments have been conducted on three real-world time series applications with 30 cross-domain scenarios. The results demonstrate that our proposed SLARDA method significantly outperforms the state-of-the-art approaches for time series domain adaptation. Our source code is available at: https://github.com/mohamedr002/SLARDA.
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http://dx.doi.org/10.1109/TNNLS.2022.3183252DOI Listing
June 2022

Effectiveness and safety of leukapheresis in hyperleukocytic leukemias: a retrospective multicenter study.

Leuk Lymphoma 2022 Jun 22:1-9. Epub 2022 Jun 22.

National Clinical Research Center for Hematologic Diseases, Jiangsu Institute of Hematology, The First Affiliated Hospital of Soochow University, Suzhou, China.

Leukapheresis is an effective adjuvant therapy for leukemia patients with hyperleukocytosis, but few studies have reported recent data with modern modalities and comparisons among different leukemia types. We conducted a retrospective study on leukapheresis among 420 patients with AML, ALL and CML in four local centers. WBC counts decreased significantly ( < 0.001) postleukapheresis in all three cohorts. Clearance efficiency was higher in acute leukemia patients than CML patients ( < 0.01). Concomitant leukocytoreduction drugs improved WBC reduction only in AML patients ( < 0.05). Leukocyte, hemoglobin and platelet levels preleukapheresis might affect the clearance efficiency in AML and/or ALL patients. Hematological toxicities were the major concerns, but most of them were mild, and only 11 patients died of all causes within one week postleukapheresis. In conclusion, leukapheresis can safely reduce the leukemic burden, especially for patients with acute leukemias.
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http://dx.doi.org/10.1080/10428194.2022.2086246DOI Listing
June 2022

MicroRNA-mediated high expression of PDIA3 was correlated with poor prognosis of patients with LUAD.

Genomics 2022 Jun 18;114(4):110417. Epub 2022 Jun 18.

Department of Pathology, Affiliated Hospital of Nantong University, Nantong, China; Medical school of Nantong University, Nantong, China. Electronic address:

Lung cancer, especially lung adenocarcinoma (LUAD) as the most common subtype has threatened the health of people. Even though more and more patients diagnosed as LUAD could be treated efficiently or even cured, a spilt of patients still suffer from disease. Here, on the basis of previous research, we firstly performed the mRNA expression of PDIA3 in pan-cancer, and differential expression between tumor and normal groups was followed. We further analyzed the survival difference and ultimately the expression of PDIA3 in LUAD was selected as our current study. Next, we investigated the mRNA and protein expression of PDIA3 from online databases and performed qRT-PCR and western blotting to verify the outcomes. We still analyzed the correlation between the expression of PDIA3 and clinicopathologic parameters and predicted the potential signal pathways as well as the possible upstream molecular of PDIA3. Considering the correlation of PDIA3 and immune infiltration, related analysis of PDIA3 and immune biomarkers along with PD-1/PD-L1, CTLA-4 were made. We clarified the expression of PDIA3 was upregulated in LUAD and its oncogenic role may be played through tumor infiltration. Thus targeting PDIA3 and immune checkpoint could enhance the efficacy of immunotherapy on patients with LUAD.
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http://dx.doi.org/10.1016/j.ygeno.2022.110417DOI Listing
June 2022

CoIn: Correlation Induced Clustering for Cognition of High Dimensional Bioinformatics Data.

IEEE J Biomed Health Inform 2022 Jun 20;PP. Epub 2022 Jun 20.

Analysis of high dimensional biomedical data such as microarray gene expression data and mass spectrometry images, is crucial to provide better medical services including cancer subtyping, protein homology detection,etc. Clustering is a fundamental cognitive task which aims to group unlabeled data into multiple clusters based on their intrinsic similarities. The K-means algorithm is one of the most widely used clustering heuristics that aims at grouping the data objects into meaningful clusters such that the sum of squared Euclidean distances within each cluster is minimized. Its conceptual simplicity and computational efficiency make it easy to be used for wide applications of different data types. However, all features of data in K-means are considered equally in relevance, which distorts the performance when clustering high-dimensional data such as microarray gene expression data, mass spectrometry images, where there exist many redundant variables and correlated variables. In this paper, we propose a new correlation induced clustering, CoIn, to capture complex correlations among high dimensional data and guarantee the correlation consistency within each cluster. We evaluate the proposed method on a high dimensional mass spectrometry dataset of liver cancer tumor to explore the metabolic differences on tissues and discover the intra-tumor heterogeneity (ITH). By comparing the results of baselines and ours, it has been found that our method produces more explainable and understandable results for clinical analysis, which demonstrates the proposed clustering paradigm has the potential with application to knowledge discovery in high dimensional bioinformatics data.
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http://dx.doi.org/10.1109/JBHI.2022.3179265DOI Listing
June 2022

Comatose Patients After Cardiopulmonary Resuscitation: An Analysis Based on Quantitative Methods of EEG Reactivity.

Front Neurol 2022 3;13:877406. Epub 2022 Jun 3.

Department of Neurology, Xuanwu Hospital, Capital Medical University, Beijing, China.

Objective: Every year, approximately 50-110/1,00,000 people worldwide suffer from cardiac arrest, followed by hypoxic-ischemic encephalopathy after cardiopulmonary resuscitation (CPR), and approximately 40-66% of patients do not recover. The purpose of this study was to identify the brain network parameters and key brain regions associated with awakening by comparing the reactivity characteristics of the brain networks between the awakening and unawakening groups of CPR patients after coma, thereby providing a basis for further awakening interventions.

Method: This study involved a prospective cohort study. Using a 64-electrode electroencephalography (EEG) wireless 64A system, EEG signals were recorded from 16 comatose patients after CPR in the acute phase (<1 month) from 2019 to 2020. MATLAB (2017b) was used to quantitatively analyze the reactivity (power spectrum and entropy) and brain network characteristics (coherence and phase lag index) after pain stimulation. The patients were divided into an awakening group and an unawakening group based on their ability to execute commands or engage in repeated and continuous purposeful behavior after 3 months. The above parameters were compared to determine whether there were differences between the two groups.

Results: (1) Power spectrum: the awakening group had higher gamma, beta and alpha spectral power after pain stimulation in the frontal and parietal lobes, and lower delta and theta spectral power in the bilateral temporal and occipital lobes than the unawakening group. (2) Entropy: after pain stimulation, the awakening group had higher entropy in the frontal and parietal lobes and lower entropy in the temporal occipital lobes than the unawakening group. (3) Connectivity: after pain stimulation, the awakening group had stronger gamma and beta connectivity in nearly the whole brain, but weaker theta and delta connectivity in some brain regions (e.g., the frontal-occipital lobe and parietal-occipital lobe) than the unawakening group.

Conclusion: After CPR, comatose patients were more likely to awaken if there was a higher stimulation of fast-frequency band spectral power, higher entropy, stronger whole-brain connectivity and better retention of frontal-parietal lobe function after pain stimulation.
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http://dx.doi.org/10.3389/fneur.2022.877406DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9205205PMC
June 2022

CRISPR/Cas9‑induced saturated mutagenesis identifies haplotype as a marker of PARP inhibitor sensitivity in breast cancer.

Mol Med Rep 2022 Aug 17;26(2). Epub 2022 Jun 17.

Department of Medical Oncology, Affiliated Hospital of Hebei University, Hebei Key Laboratory of Cancer Radiotherapy and Chemotherapy, Baoding, Hebei 071000, P.R. China.

Breast cancer treatment with poly(ADP‑ribose)polymerase (PARP) inhibitors is currently limited to cells defective in the homologous recombination repair (HRR) pathway. The chemical inhibition of many HRR deficiency genes may sensitize cancer cells to PARP inhibitors. In the present study, , a central player in the HRR pathway, was selected to explore additional low variation and highly representative markers for PARP inhibitor activity. A CRISPR/Cas9‑based saturated mutation approach for the WALKER domain was used to evaluate the sensitivity of the PARP inhibitor olaparib. Five amino acid mutation sites were identified in olaparib‑resistant cells. Two haplotypes were assembled from the mutations, and may represent useful pharmacogenomic markers of PARP inhibitor sensitivity.
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http://dx.doi.org/10.3892/mmr.2022.12774DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9309539PMC
August 2022

Closed-loop transcranial ultrasound stimulation with a fuzzy controller for modulation of motor response and neural activity of mice.

J Neural Eng 2022 Jun 30;19(3). Epub 2022 Jun 30.

State Key Laboratory of Cognitive Neuroscience and Learning, Beijing Normal University, Beijing 100875, People's Republic of China.

. We propose a closed-loop transcranial ultrasound stimulation (TUS) with a fuzzy controller to realize real-time and precise control of the motor response and neural activity of mice.. The mean absolute value (MAV) of the electromyogram (EMG) and peak value (PV) of the local field potential (LFP) were measured under different ultrasound intensities. A model comprising the characteristics of the MAV of the EMG, PV of the LFP, and ultrasound intensity was built using a neural network, and a fuzzy controller, proportional-integral-derivative (PID) controller, and immune feedback controller were proposed to adjust the ultrasound intensity using the feedback of the EMG MAV and the LFP PV.. In simulation, the quantitative calculation indicated that the maximum relative errors between the simulated EMG MAV and the expected values were 17% (fuzzy controller), 110% (PID control), 66% (immune feedback control); furthermore, the corresponding values of the LFP PV were 12% (fuzzy controller), 53% (PID control), 55% (immune feedback control). The average relative errors of fuzzy controller, PID control, immune feedback control were 4.97%, 13.15%, 11.52%, in the EMG closed-loop experiment and 7.76%, 11.84%, 13.56%, in the LFP closed-loop experiment.. The simulation and experimental results demonstrate that the closed-loop TUS with a fuzzy controller can realize the tracking control of the motor response and neural activity of mice.
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http://dx.doi.org/10.1088/1741-2552/ac7893DOI Listing
June 2022

Deep EEG Superresolution via Correlating Brain Structural and Functional Connectivities.

IEEE Trans Cybern 2022 Jun 14;PP. Epub 2022 Jun 14.

Electroencephalogram (EEG) excels in portraying rapid neural dynamics at the level of milliseconds, but its spatial resolution has often been lagging behind the increasing demands in neuroscience research or subject to limitations imposed by emerging neuroengineering scenarios, especially those centering on consumer EEG devices. Current superresolution (SR) methods generally do not suffice in the reconstruction of high-resolution (HR) EEG as it remains a grand challenge to properly handle the connection relationship amongst EEG electrodes (channels) and the intensive individuality of subjects. This study proposes a deep EEG SR framework correlating brain structural and functional connectivities (Deep-EEGSR), which consists of a compact convolutional network and an auxiliary fully connected network for filter generation (FGN). Deep-EEGSR applies graph convolution adapting to the structural connectivity amongst EEG channels when coding SR EEG. Sample-specific dynamic convolution is designed with filter parameters adjusted by FGN conforming to functional connectivity of intensive subject individuality. Overall, Deep-EEGSR operates on low-resolution (LR) EEG and reconstructs the corresponding HR acquisitions through an end-to-end SR course. The experimental results on three EEG datasets (autism spectrum disorder, emotion, and motor imagery) indicate that: 1) Deep-EEGSR significantly outperforms the state-of-the-art counterparts with normalized mean squared error (NMSE) decreased by 1% - 6% and the improvement of signal-to-noise ratio (SNR) up to 1.2 dB and 2) the SR EEG manifests superiority to the LR alternative in ASD discrimination and spatial localization of typical ASD EEG characteristics, and this superiority even increases with the scale of SR.
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http://dx.doi.org/10.1109/TCYB.2022.3178370DOI Listing
June 2022

Discoidin domain receptor 1 may be involved in biological barrier homeostasis.

J Clin Pharm Ther 2022 Jun 4. Epub 2022 Jun 4.

Department of Gastroenterology, Key Laboratory of Digestive Diseases, LanZhou University Second Hospital, LanZhou University, Lanzhou, China.

What Is Known And Objective: Discoidin domain receptor 1 (DDR1) is a receptor tyrosine kinase involved in the pathological processes of several diseases, such as keloid formation, renal fibrosis, atherosclerosis, tumours, and inflammatory processes. The biological barrier is the first line of defence against pathogens, and its disruption is closely related to diseases. In this review, we attempt to elucidate the relationship between DDR1 and the biological barrier, explore the potential biological value of DDR1, and review the current research status and clinical potential of DDR1-selective inhibitors.

Methods: We conducted an extensive literature search on PubMed to collect studies on the relevance of DDR1 to biological barriers and DDR1-selective inhibitors. With these studies, we explored the relationship between DDR1 and biological barriers and briefly reviewed representative DDR1-selective inhibitors that have been reported in recent years.

Results And Discussion: First, the review of the potential mechanisms by which DDR1 regulates biological barriers, including the epithelial, vascular, glomerular filtration, blood-labyrinth, and blood-brain barriers. In the body, DDR1 dysfunction and aberrant expression may be involved in the homeostasis of the biological barrier. Secondly, the review of DDR1 inhibitors reported in recent years shows that DDR1-targeted inhibition is an attractive and promising pharmacological intervention.

What Is New And Conclusions: This review shows that DDR1 is involved in various physiological and pathological processes and in the regulation of biological barrier homeostasis. However, studies on DDR1 and biological barriers are still scarce, and further studies are needed to elucidate their specific mechanisms. The development of targeted inhibitors provides a new direction and idea to study the mechanism of DDR1.
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http://dx.doi.org/10.1111/jcpt.13705DOI Listing
June 2022

InflamNat: web-based database and predictor of anti-inflammatory natural products.

J Cheminform 2022 Jun 4;14(1):30. Epub 2022 Jun 4.

Key Laboratory of Medicinal Chemistry for Natural Resource, Ministry of Education; Yunnan Provincial Center for Research & Development of Natural Products, School of Chemical Science and Technology, and School of Software, Yunnan University, Kunming, 650091, China.

Natural products (NPs) are a valuable source for anti-inflammatory drug discovery. However, they are limited by the unpredictability of the structures and functions. Therefore, computational and data-driven pre-evaluation could enable more efficient NP-inspired drug development. Since NPs possess structural features that differ from synthetic compounds, models trained with synthetic compounds may not perform well with NPs. There is also an urgent demand for well-curated databases and user-friendly predictive tools. We presented a comprehensive online web platform (InflamNat, http://www.inflamnat.com/ or http://39.104.56.4/ ) for anti-inflammatory natural product research. InflamNat is a database containing the physicochemical properties, cellular anti-inflammatory bioactivities, and molecular targets of 1351 NPs that tested on their anti-inflammatory activities. InflamNat provides two machine learning-based predictive tools specifically designed for NPs that (a) predict the anti-inflammatory activity of NPs, and (b) predict the compound-target relationship for compounds and targets collected in the database but lacking existing relationship data. A novel multi-tokenization transformer model (MTT) was proposed as the sequential encoder for both predictive tools to obtain a high-quality representation of sequential data. The experimental results showed that the proposed predictive tools achieved an AUC value of 0.842 and 0.872 in the prediction of anti-inflammatory activity and compound-target interactions, respectively.
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http://dx.doi.org/10.1186/s13321-022-00608-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9167499PMC
June 2022

Comparative Transcriptomics Unveil the Crucial Genes Involved in Coumarin Biosynthesis in Dunn.

Front Plant Sci 2022 17;13:899819. Epub 2022 May 17.

College of Biological and Pharmaceutical Engineering, West Anhui University, Lu'an, China.

Dunn is a commonly used traditional Chinese medicine that is abundant in furano- and dihydropyrano coumarins. When reaches the bolting stage, the roots gradually lignified, and the content of coumarins declines rapidly. Non-bolting has always been a decisive factor for harvesting the materials. To evaluate the amount of coumarin components in unbolted and bolted , the variations of praeruptorin A, praeruptorin B, praeruptorin E, peucedanocoumarin I, and peucedanocoumarin II were determined. Additionally, 336,505 transcripts were obtained from the comparative transcriptome data. Among them, a total of 1,573 differentially expressed genes were screened out. To identify the critical genes involved in coumarin biosynthesis, comparative transcriptomics coupled with co-expression associated analysis was conducted. Finally, coumarin biosynthesis-related eighteen candidate genes were selected for the validation of PCR. Additionally, a phylogenetic tree and the expression profile of ATP-binding cassette (ABC) transporters were constructed. To clarify the main genes in the regulation of coumarin biosynthesis, the interaction network of the co-expression genes from thirteen modules was constructed. Current results exhibited the significant increment of praeruptorin A, praeruptorin B and praeruptorin E in the bolted . Although, peucedanocoumarin I and peucedanocoumarin II were slightly increased. Besides the content of coumarins, the essential genes involved in the coumarin biosynthesis also exhibited an overall downward trend after bolting. Three () involved in the production of lignin monomers had been demonstrated to be downregulated. , , , , , and some ABC transporters were dramatically downregulated at the bolting stage. These results indicated that the downregulation of coumarin biosynthetic genes in the bolted ultimately reduced the formation of coumarins. However, the mechanism through which bolting indirectly affects the formation of coumarin still needs extra functional verification.
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http://dx.doi.org/10.3389/fpls.2022.899819DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9152428PMC
May 2022

Standing strong amid a pandemic: How a global online team project stands up to the public health crisis.

Br J Educ Technol 2022 May 10;53(3):577-592. Epub 2022 Feb 10.

Dyson School of Applied Economics and Management Cornell University Ithaca USA.

The annual instructional virtual team Project X brings together professors and students from across the globe to engage in client projects. The 2020 project was challenged by the global disruption of the COVID-19 pandemic. This paper draws on a quantitative dataset from a post-project survey among 500 participating students and a qualitative narrative inquiry of personal experiences of the faculty members. The findings reveal how innovative use of a variety of collaboration and communication technologies helped students and their professors in building emotional connection and compassion to support each other in the midst of the crisis, and to accomplish the project despite connectivity disruptions. The results suggest that the role of an instructor changed to a coach and mentor, and technology was used to create a greater sense of inclusion and co-presence in student-faculty interactions. Ultimately, the paper highlights the role of technology to help the participants navigate sudden crisis affecting a global online instructional team project. The adaptive instructional teaching strategies and technologies depicted in this study offer transformative potential for future developments in higher education.
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http://dx.doi.org/10.1111/bjet.13189DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9111488PMC
May 2022

Structure-based discovery and development of novel O-GlcNAcase inhibitors for the treatment of Alzheimer's disease.

Eur J Med Chem 2022 Aug 13;238:114444. Epub 2022 May 13.

College of Pharmacy and Research Institute of Pharmaceutical Sciences, Chonnam National University, Gwangju, 61186, Republic of Korea. Electronic address:

The neurofibrillary tangles (NFTs) formed from hyperphosphorylation of tau protein are closely associated with Alzheimer's disease (AD). O-GlcNAcylation of tau can negatively regulate hyperphosphorylation and the O-GlcNAcase (OGA) catalyzes the removal of O-linked β-N-acetylglucosamine (O-GlcNAc) from tau protein. Therefore, preventing tau hyperphosphorylation by increasing the levels of tau O-GlcNAcylation via OGA inhibitors could be a promising approach. Based on Thiamet-G, a potent OGA inhibitor, and its binding mode to OGA, a novel OGA inhibitor scaffold bearing three parts was designed and hit compound 7j was successfully identified via extensive exploring. Further chemical optimization and diversification of the 7j structure resulted in compound 39 which possesses excellent OGA inhibition, no cytotoxicity, and has good pharmacokinetic properties. In acute AD model mice, 39 was more effective than Thiamet-G in inhibiting OGA activity attributable to its better blood-brain barrier permeability. In addition, 39 restored the cognitive function in mice and reduced amyloid-β (Aβ) concentrations to a greater extent than Thiamet-G. Molecular docking studies demonstrated that 39 was well associated with OGA through H-bonds and hydrophobic interaction. Together, these findings suggest that 39 was promising as a potent OGA inhibitor in the treatment of AD.
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http://dx.doi.org/10.1016/j.ejmech.2022.114444DOI Listing
August 2022

Co-Crystal of Rosiglitazone With Berberine Ameliorates Hyperglycemia and Insulin Resistance Through the PI3K/AKT/TXNIP Pathway and .

Front Pharmacol 2022 28;13:842879. Epub 2022 Apr 28.

Department of Pharmacology, College of Pharmacy, Chongqing Medical University, Chongqing, China.

Type 2 diabetes mellitus (T2DM) is a chronic metabolic disease characterized by insulin resistance and hyperglycemia. This study examined the effect and elucidated the mechanism of improvement of hyperglycemia and insulin resistance by a co-crystal of rosiglitazone with berberine (RB) in high-sugar high-fat diet (HSHFD)-induced diabetic KKAy mice. Diabetic KKAy mice were randomly divided into seven groups: KKAy model control group (DM control) treated with 3% sodium carboxymethyl cellulose; RB groups, administered daily with RB 0.7 mg/kg (RB-L), 2.11 mg/kg (RB-M), or 6.33 mg/kg (RB-H); positive control groups, administered daily with rosiglitazone 1.04 mg/kg (RSG), berberine 195 mg/kg (BBR), or combination of 1.04 mg/kg RSG and 1.08 mg/kg BBR (MIX). Test compounds were administered orally for 8 weeks. Non-diabetic C57BL/6J mice were used as normal control (NC). Blood glucose, food intake, body weight, glucose-lipid metabolism, and pathological changes in the pancreas and liver were examined. We further evaluated the mechanism of action of RB in C2C12 and HepG2 cells stimulated with high glucose and palmitate. RB treatment improved glucolipid metabolism and insulin resistance in diabetic KKAy mice. RB reduced blood glucose levels, white fat index, plasma triglyceride (TG), low-density lipoprotein (LDL), gastric inhibitory peptide (GIP), and insulin levels, increased the levels of plasma glucagon-like peptide-1 (GLP-1), high-density lipoprotein (HDL), and glycogen content in the liver and muscle; and improved oral glucose tolerance test (OGTT), insulin tolerance test (ITT), and pathological changes in the pancreas and liver of KKAy mice. Moreover, RB upregulated p-PI3K and p-AKT levels and reduced TXNIP expression in KKAy mice and in HepG2 and C2C12 cells. These data indicate that RB ameliorates insulin resistance and metabolic disorders, and the mechanism might be through regulating the PI3K/AKT/TXNIP signaling pathway Thus, the co-crystal drug RB may be considered as a potential antidiabetic agent for future clinical therapy.
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http://dx.doi.org/10.3389/fphar.2022.842879DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9096649PMC
April 2022

Screening of and mechanism underlying the action of serum- and glucocorticoid-regulated kinase 3-targeted drugs against estrogen receptor-positive breast cancer.

Eur J Pharmacol 2022 Jul 13;927:174982. Epub 2022 May 13.

Department of Pharmacology, College of Pharmacy, Chongqing Medical University, Chongqing, 400016, China; Chongqing Key Laboratory of Drug Metabolism, Chongqing, 400016, China; Key Laboratory for Biochemistry and Molecular Pharmacology of Chongqing, Chongqing, 400016, China. Electronic address:

Breast cancer is the most common cancer in women. Serum and glucocorticoid-regulated kinase 3 (SGK3) promotes the progression and drug resistance of estrogen receptor-positive (ER+) breast cancer. Therefore, SGK3 is a promising therapeutic target for the treatment of ER + breast cancer. In this study, we used computer-aided drug discovery/design to perform a virtual screening of SGK3 inhibitors from the ZINC database. The results of MTT assay, real-time cell proliferation analysis, colony formation assay, transwell migration assay, and orthotopic implantation model show that Zinc-09 inhibited the proliferation and migration of ER + breast cancer cells in vivo and in vitro. Furthermore, Zinc-09 decreased SGK3 expression, and knockdown of SGK3 by siRNA reversed the inhibitory effect of Zinc-09 in MCF-7 cells. Moreover, Zinc-09 treatment induced G1 phase arrest and autophagic cell death. Taken together, Zinc-09 can suppress ER + breast cancer. This study provides an experimental and theoretical basis for the research and development of new anti-ER + breast cancer drugs.
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http://dx.doi.org/10.1016/j.ejphar.2022.174982DOI Listing
July 2022

Preparation and Properties of Cyclodextrin Inclusion Complexes of .

Molecules 2022 Apr 25;27(9). Epub 2022 Apr 25.

College of Agronomy and Agricultural Sciences, Liaocheng University, Liaocheng 252000, China.

In order to improve the aqueous solubility and enhance the bioavailability of (Hyp), three inclusion complexes (ICs) of Hyp with 2-hydroxypropyl-β-cyclodextrin (2H-β-CD), β-cyclodextrin (β-CD), and methyl-β-cyclodextrin (M-β-CD) were prepared using the ultrasonic method. The characterization of the inclusion complexes (ICs) was achieved using Fourier-transform infrared spectroscopy (FTIR), scanning electronic microscopy (SEM), X-ray powder diffraction (XRPD), thin-layer chromatography (TLC), and H nuclear magnetic resonance (H NMR). The effects of the ICs on the solubility and antioxidant activity of Hyp were investigated. A Job's plot revealed that the Hyp formed ICs with three kinds of cyclodextrin (CD), all at a 1:1 stoichiometric ratio. The FTIR, SEM, XRPD, TLC, and H NMR results confirmed the formation of inclusion complexes. The water solubility of the IC of Hyp with 2-hydroxypropyl-β-cyclodextrin was enhanced 9-fold compared to the solubility of the original Hyp. The antioxidant activity tests showed that the inclusion complexes had higher antioxidant activities compared to free Hyp in vitro and the HO-RAW264.7 cell model. Therefore, encapsulation with CDs can not only improve Hyp's water solubility but can also enhance its biological activity, which provides useful information for the potential application of complexation with Hyp in a clinical context.
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http://dx.doi.org/10.3390/molecules27092761DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9100073PMC
April 2022
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