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Identification of formononetin as the active compound of CR-SR in hepatocellular carcinoma treatment: An integrated approach combining network pharmacology and weighted gene co-expression networks.
Li, C, Xie, Y, Hu, S, Yu, H, Xu, Y, Shen, H, Yuan, Y, Gu, L, Pu, B
Chemical biology & drug design. 2024;(1):e14363
Abstract
Hepatocellular carcinoma (HCC) is a life-threatening disease for which there is no cure. Traditional Chinese medicine is a treasure trove of Medicinals that has been used for thousands of years. In China, the traditional herb pair, Curcumae Rhizoma and Sparganii Rhizoma (CR-SR) represent a classic herbal combination used for the treatment of HCC. However, the drug targets and pharmacological mechanism of action of CR-SR in the treatment of HCC are unclear. To address this, we screened the active components and drug targets of CR-SR from the Traditional Chinese Medicine Systems Pharmacology (TCMSP) database and a high-throughput experiment- and reference-guided database of traditional Chinese medicines (HERB database). Combined with the weighted co-expression network analysis of dataset GSE76427, we constructed an active component-target-disease regulatory network. It was found that CR-SR's active components for HCC treatment included trans-gondoic acid, beta-sitosterol, stigmasterol, hederagenin, and formononetin. These compounds specifically targeted the genes Estrogen Receptor 1 (ESR1), Cyclin A2 (CCNA2), Checkpoint Kinase 1 (CHEK1), and Nuclear Receptor Coactivator 2 (NCOA2). ESR1, CCNA2, and CHEK1 genes showed significant differences in survival prognosis, expression levels, and statistical significance during the pathological stage. Moreover, their high affinity for formononetin was determined through molecular docking analysis. Cell assays and high-throughput sequencing were performed to reveal that the inhibitory effect of formononetin on HepG2 cell proliferation was related to hepatocyte metabolism and cell cycle regulation-related pathways. This study provides insights into potential HCC treatments.
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BISCUIT: an efficient, standards-compliant tool suite for simultaneous genetic and epigenetic inference in bulk and single-cell studies.
Zhou, W, Johnson, BK, Morrison, J, Beddows, I, Eapen, J, Katsman, E, Semwal, A, Habib, WA, Heo, L, Laird, PW, et al
Nucleic acids research. 2024;(6):e32
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Abstract
Data from both bulk and single-cell whole-genome DNA methylation experiments are under-utilized in many ways. This is attributable to inefficient mapping of methylation sequencing reads, routinely discarded genetic information, and neglected read-level epigenetic and genetic linkage information. We introduce the BISulfite-seq Command line User Interface Toolkit (BISCUIT) and its companion R/Bioconductor package, biscuiteer, for simultaneous extraction of genetic and epigenetic information from bulk and single-cell DNA methylation sequencing. BISCUIT's performance, flexibility and standards-compliant output allow large, complex experimental designs to be characterized on clinical timescales. BISCUIT is particularly suited for processing data from single-cell DNA methylation assays, with its excellent scalability, efficiency, and ability to greatly enhance mappability, a key challenge for single-cell studies. We also introduce the epiBED format for single-molecule analysis of coupled epigenetic and genetic information, facilitating the study of cellular and tissue heterogeneity from DNA methylation sequencing.
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Radioiodine-refractory differentiated thyroid cancer: Molecular mechanisms and therapeutic strategies for radioiodine resistance.
Shen, H, Zhu, R, Liu, Y, Hong, Y, Ge, J, Xuan, J, Niu, W, Yu, X, Qin, JJ, Li, Q
Drug resistance updates : reviews and commentaries in antimicrobial and anticancer chemotherapy. 2024;:101013
Abstract
Radioiodine-refractory differentiated thyroid cancer (RAIR-DTC) is difficult to treat with radioactive iodine because of the absence of the sodium iodide transporter in the basement membrane of thyroid follicular cells for iodine uptake. This is usually due to the mutation or rearrangement of genes and the aberrant activation of signal pathways, which result in abnormal expression of thyroid-specific genes, leading to resistance of differentiated thyroid cancer cells to radioiodine therapy. Therefore, inhibiting the proliferation and growth of RAIR-DTC with multikinase inhibitors and other drugs or restoring its differentiation and then carrying out radioiodine therapy have become the first-line treatment strategies and main research directions. The drugs that regulate these kinases or signaling pathways have been studied in clinical and preclinical settings. In this review, we summarized the major gene mutations, gene rearrangements and abnormal activation of signaling pathways that led to radioiodine resistance of RAIR-DTC, as well as the medicine that have been tested in clinical and preclinical trials.
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Distribution and roles of Ligilactobacillus murinus in hosts.
Chuandong, Z, Hu, J, Li, J, Wu, Y, Wu, C, Lai, G, Shen, H, Wu, F, Tao, C, Liu, S, et al
Microbiological research. 2024;:127648
Abstract
Ligilactobacillus murinus, a member of the Ligilactobacillus genus, holds significant potential as a probiotic. While research on Ligilactobacillus murinus has been relatively limited compared to well-studied probiotic lactic acid bacteria such as Limosilactobacillus reuteri and Lactobacillus gasseri, a mounting body of evidence highlights its extensive involvement in host intestinal metabolism and immune activities. Moreover, its abundance exhibits a close correlation with intestinal health. Notably, beyond the intestinal context, Ligilactobacillus murinus is gaining recognition for its contributions to metabolism and regulation in the oral cavity, lungs, and vagina. As such, Ligilactobacillus murinus emerges as a potential probiotic candidate with a pivotal role in supporting host well-being. This review delves into studies elucidating the multifaceted roles of Ligilactobacillus murinus. It also examines its medicinal potential and associated challenges, underscoring the imperative to delve deeper into unraveling the mechanisms of its actions and exploring its health applications.
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Severe megaloblastic anemia in a patient with advanced lung adenocarcinoma during treatment with erlotinib: a case report and literature review.
Yan, X, Kong, J, Wang, J, Wang, C, Shen, H
BMC pulmonary medicine. 2024;(1):121
Abstract
BACKGROUND Erlotinib is a first-generation, tyrosine kinase inhibitor of the epidermal growth factor receptor (EGFR-TKI) used for the treatment patients with NSCLC. Erlotinib is considered as a safe and effective treatment option, with generally good tolerance. Diarrhea and rash are the most common side effects, and more rare side effects appear in long-term real-world applications. Severe erlotinib related megaloblastic anemia is rare and remains unreported. This is the first case report of severe megaloblastic anemia in a patient with advanced lung adenocarcinoma with an EGFR L858R mutation treated with erlotinib. In this report, the clinical manifestations, diagnosis and treatment of erlotinib related severe megaloblastic anemia are described, and the possible pathogenesis and related treatment options are discussed. CASE DESCRIPTION Herein, we present a 57- year-old non-smoking female diagnosed with metastatic lung adenocarcinoma harboring an EGFR L858R mutation, who had received erlotinib as the first-line therapy. After 44 weeks of treatment, the patient developed severe anemia. Anemia was manifested as megaloblastic anemia with elevated mean corpuscular volume and mean corpuscular hemoglobin. The total vitamin B12 level was below the detection limit of 50.00 pg /mL. Bone marrow smear suggested megaloblastic anemia. Her hematologic parameters were markedly recovered following the withdrawal of erlotinib and vitamin B12 supplement. As a result, the patient was diagnosed with erlotinib-associated megaloblastic anemia. CONCLUSIONS This is the first case of severe megaloblastic anemia reported with erlotinib. Few of these hematologic adverse effects have been observed in studies on erlotinib, this case report highlights this possibility for long-term erlotinib administration. Close clinical and blood monitoring is recommended for patients receiving long-term TKI therapy.
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Development of packaging films based on UiO-66 MOF loaded melatonin with antioxidation functions for spinach preservation.
Wang, M, Xu, J, Li, L, Shen, H, Ding, Z, Xie, J
Food chemistry. 2024;:138211
Abstract
Spinach tends to deteriorate after harvest due to physiological metabolic activities. As a natural, pollution-free, and environmentally friendly preservative, melatonin (MT) can effectively maintain the quality of fruits and vegetables after harvest and delay senescence. To enhance the preservation effect of MT, this study developed antioxidant films using MT-loaded UiO-66 metal-organic framework (MOF) nanoparticles. This approach effectively extends the shelf life of spinach while preserving its quality. The underlying mechanism involves leveraging the microporous structure and stability of UiO-66 MOF. Experimental results obtained from the packaging films demonstrated significant improvements in both mechanical strength and antioxidant properties when UiO-66 was loaded with MT at a concentration of 0.20 mg/mL and combined with sodium alginate. Freshness preservation experiments also indicated the effective preservation effect of these films on spinach. In conclusion, the results of this study suggest that MT-loaded UiO-66 MOF is a promising active packaging material for spinach preservation.
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International clinical practice guideline on the use of traditional Chinese medicine for ulcerative colitis by Board of Specialty Committee of Digestive System Disease of World Federation of Chinese Medicine Societies (2023).
Zhang, S, Zhao, L, Shen, H, Tang, Z, Qin, D, Li, J, Zhang, B, Yang, G, Chen, M, Wu, K, et al
Phytotherapy research : PTR. 2024;(2):970-999
Abstract
Ulcerative colitis (UC), a chronic and nonspecific inflammatory disease of the intestine, has become a prevalent global health concern. This guideline aims to equip clinicians and caregivers with effective strategies for the treatment and management of adult UC patients using traditional Chinese medicine (TCM). The guideline systematically evaluated contemporary evidence through the Grading of Recommendations Assessment, Development, and Evaluation framework. Additionally, it incorporated insights from ancient Chinese medical sources, employing the evidence grading method found in traditional TCM literature. The development process involved collaboration with multidisciplinary experts and included input from patients with UC. The guideline, based on a comprehensive review of available evidence, present 40 recommendations. They offer a condensed overview of TCM's role in understanding the pathogenesis, diagnosis, and treatment of UC, along with an assessment of the efficacy of various TCM-based treatments. TCM exhibits promising outcomes in the treatment of UC. However, to establish its efficacy conclusively, further high-quality clinical studies on TCM for UC are essential.
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Viral lysing can alleviate microbial nutrient limitations and accumulate recalcitrant dissolved organic matter components in soil.
Tong, D, Wang, Y, Yu, H, Shen, H, Dahlgren, RA, Xu, J
The ISME journal. 2023;(8):1247-1256
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Abstract
Viruses are critical for regulating microbial communities and biogeochemical processes affecting carbon/nutrient cycling. However, the role of soil phages in controlling microbial physiological traits and intrinsic dissolved organic matter (DOM) properties remains largely unknown. Herein, microcosm experiments with different soil phage concentrates (including no-added phages, inactive phages, and three dilutions of active phages) at two temperatures (15 °C and 25 °C) were conducted to disclose the nutrient and DOM dynamics associated with viral lysing. Results demonstrated three different phases of viral impacts on CO2 emission at both temperatures, and phages played a role in maintaining Q10 within bounds. At both temperatures, microbial nutrient limitations (especially P limitation) were alleviated by viral lysing as determined by extracellular enzyme activity (decreased Vangle with active phages). Additionally, the re-utilization of lysate-derived DOM by surviving microbes stimulated an increase of microbial metabolic efficiency and recalcitrant DOM components (e.g., SUV254, SUV260 and HIX). This research provides direct experimental evidence that the "viral shuttle" exists in soils, whereby soil phages increase recalcitrant DOM components. Our findings advance the understanding of viral controls on soil biogeochemical processes, and provide a new perspective for assessing whether soil phages provide a net "carbon sink" vs. "carbon source" in soils.
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The ABCB1 C3435T Polymorphism is Associated with Triglyceride Reduction in Atorvastatin-treated Uygur Patients with Coronary Heart Disease and Dyslipidemia: An Observational Study.
Wang, T, Wu, J, Liu, T, Xu, L, Feng, J, Zhang, H, Shen, H, Sun, L, Li, H, Yu, L
Endocrine, metabolic & immune disorders drug targets. 2023;(9):1215-1228
Abstract
BACKGROUND The morbidity of coronary heart disease (CHD) and dyslipidemia in the Uygur population of Xinjiang is higher than the national average. Interindividual variability of the response to atorvastatin is a major clinical problem; generally, statins shed less impressive benefits for females than males. Nevertheless, it is unclear whether ABCB1 genes and sex modify the efficacy of atorvastatin in Uygur patients. OBJECTIVE To determine the impact of ABCB1 gene polymorphisms on the therapeutic response to atorvastatin in a Uygur population with dyslipidemia. METHODS Patients with dyslipidemia were treated with 20 mg/d or 40 mg/d atorvastatin for two to six months. TC, LDL-C, HDL-C, TG, APOB, APOE, LP(a), and APOA1 levels were measured before and after atorvastatin administration. We performed genotyping of ABCB1 C3435T and G2677T variants using hybridization sequencing. The association of variants between the percentage of change in TG levels was examined using multiple linear regression analysis. RESULTS We enrolled 193 Uygur patients. Atorvastatin reduced TG, LDL-C, TC, APOB, and APOE levels (P < 0.05), whereas LP(a) and APOA1 levels increased (P < 0.05). In multiple linear regression analysis, baseline TG level (beta 0.204; 95% confidence interval (CI): 1.980-10.493; P = 0.004) and TT genotype of ABCB1 C3435T (beta 0.162; 95% CI: 2.517-23.406; P = 0.023) predicted TG reduction with atorvastatin therapy in overall patients. Baseline TG level (beta 0.346; 95% CI: 4.374 -13.34; P < 0.001) with the TT genotype of ABCB1 C3435T (beta 0.401; 95% CI: 4.053-28.356; P = 0.021) was associated with a significant reduction in TG levels in men. Only baseline TG level predicted TG reduction within six months of atorvastatin therapy for females (beta 0.61; 95% CI: 3.204-20.557; P = 0.041). CONCLUSION In patients with the ABCB1 C3435T TT genotype, atorvastatin more effectively lowered TG than other polymorphisms. This investigation may provide insights into effective individualized therapies for CHD and dyslipidemia in the Uygur population.
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Simulating the isotropic Raman spectra of O-H stretching mode in liquid H2O based on a machine learning potential: the influence of vibrational couplings.
Shen, H, Shen, X, Wu, Z
Physical chemistry chemical physics : PCCP. 2023;(41):28180-28188
Abstract
In this study, we trained a deep potential (DP) for H2O, an accurate machine learning (ML) potential. We performed molecular dynamics (MD) simulations of liquid water using the DP model (or DeePMD simulations). Our results showed that the DP model exhibits DFT-level accuracy, and the DeePMD simulation is a promising approach for modeling the structural properties of liquid water. Based on the DeePMD simulation trajectories, we calculated the isotropic Raman spectra of the O-H stretching mode using the surface-specific velocity-velocity correlation function (ssVVCF), showing that the DeePMD/ssVVCF approach can correctly capture the bimodal characteristics of the experimental Raman spectra, with one peak located near 3400 cm-1 and the other near 3250 cm-1. The success of the DeePMD/ssVVCF approach should be credited to (1) the DFT-level accuracy of the DP model for H2O, (2) the ssVVCF formulation considering the coupling between vibrational modes, and (3) non-Condon effects. Furthermore, the DeePMD simulations revealed that the anharmonic interactions between the coupled water molecules in the first and second hydration shells should play an essential role in the strong mixing of the H-O-H bending mode and the O-H stretching mode, leading to the delocalization of the O-H stretching band. In particular, increasing the strength of hydrogen bonds would enhance the bend-stretch coupling, leading to the red-shifting of the O-H vibrational spectra and the increase in the intensity of the shoulder around 3250 cm-1.