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1.
Open Forum Infect Dis ; 11(5): ofae238, 2024 May.
Article in English | MEDLINE | ID: mdl-38770210

ABSTRACT

Varied seasonal patterns of respiratory syncytial virus (RSV) have been reported worldwide. We conducted a systematic review on articles identified in PubMed reporting RSV seasonality based on data collected before 1 January 2020. RSV seasonal patterns were examined by geographic location, calendar month, analytic method, and meteorological factors including temperature and absolute humidity. Correlation and regression analyses were conducted to explore the relationship between RSV seasonality and study methods and characteristics of study locations. RSV seasons were reported in 209 articles published in 1973-2023 for 317 locations in 77 countries. Regular RSV seasons were similarly reported in countries in temperate regions, with highly variable seasons identified in subtropical and tropical countries. Longer durations of RSV seasons were associated with a higher daily average mean temperature and daily average mean absolute humidity. The global seasonal patterns of RSV provided important information for optimizing interventions against RSV infection.

2.
Nat Commun ; 15(1): 2939, 2024 Apr 05.
Article in English | MEDLINE | ID: mdl-38580630

ABSTRACT

Endplate sclerosis is a notable aspect of spine degeneration or aging, but the mechanisms remain unclear. Here, we report that senescent macrophages accumulate in the sclerotic endplates of lumbar spine instability (LSI) or aging male mouse model. Specifically, knockout of cdkn2a (p16) in macrophages abrogates LSI or aging-induced angiogenesis and sclerosis in the endplates. Furthermore, both in vivo and in vitro studies indicate that IL-10 is the primary elevated cytokine of senescence-related secretory phenotype (SASP). Mechanistically, IL-10 increases pSTAT3 in endothelial cells, leading to pSTAT3 directly binding to the promoters of Vegfa, Mmp2, and Pdgfb to encourage their production, resulting in angiogenesis. This study provides information on understanding the link between immune senescence and endplate sclerosis, which might be useful for therapeutic approaches.


Subject(s)
Cellular Senescence , Interleukin-10 , Animals , Male , Mice , Angiogenesis , Endothelial Cells , Interleukin-10/genetics , Macrophages , Sclerosis
3.
Cancer Cell Int ; 24(1): 131, 2024 Apr 09.
Article in English | MEDLINE | ID: mdl-38594722

ABSTRACT

Extensive exploration of the molecular subtypes of triple-negative breast cancer (TNBC) is critical for advancing precision medicine. Notably, the luminal androgen receptor (LAR) subtype has attracted attention for targeted treatment combining androgen receptor antagonists and CDK4/6 inhibitors. Unfortunately, this strategy has proven to be of limited efficacy, highlighting the need for further optimization. Using our center's comprehensive multiomics dataset (n = 465), we identified novel therapeutic targets and evaluated their efficacy through multiple models, including in vitro LAR cell lines, in vivo cell-derived allograft models and ex vivo patient-derived organoids. Moreover, we conducted flow cytometry and RNA-seq analysis to unveil potential mechanisms underlying the regulation of tumor progression by these therapeutic strategies. LAR breast cancer cells exhibited sensitivity to chidamide and enzalutamide individually, with a drug combination assay revealing their synergistic effect. Crucially, this synergistic effect was verified through in vivo allograft models and patient-derived organoids. Furthermore, transcriptomic analysis demonstrated that the combination therapeutic strategy could inhibit tumor progression by regulating metabolism and autophagy. This study confirmed that the combination of histone deacetylase (HDAC) inhibitors and androgen receptor (AR) antagonists possessed greater therapeutic efficacy than monotherapy in LAR TNBC. This finding significantly bolsters the theoretical basis for the clinical translation of this combination therapy and provides an innovative strategy for the targeted treatment of LAR TNBC.

4.
Front Public Health ; 12: 1374522, 2024.
Article in English | MEDLINE | ID: mdl-38584914

ABSTRACT

Background: Mobile phone addiction has adverse influences on the physical and mental health of college students. However, few studies shed light on the effect of fear of missing out on mobile phone addiction and the underlying mechanisms among college students. Methods: To explore their associations, the present study used the Fear of Missing Out Scales (FoMOS), Loneliness Scale (USL-8), Mobile Phone Addiction Index Scale (MPAI), and Depression-Anxiety-Stress Questionnaire (DASS-21) to investigate 750 college students. Results: The results suggested that fear of missing out significantly positively predicted mobile phone addiction. This direct effect could be mediated by depression, and the indirect effect of fear of missing out on mobile phone addiction could be moderated by loneliness. Specifically, the indirect effect was stronger for students with high levels of loneliness. Conclusion: This study provides a theoretical basis for developing future interventions for mobile phone addiction in higher education students.


Subject(s)
Depression , Loneliness , Humans , Fear , Students , Technology Addiction
5.
Medicine (Baltimore) ; 103(14): e37683, 2024 Apr 05.
Article in English | MEDLINE | ID: mdl-38579075

ABSTRACT

Since the emergence of the Coronavirus Disease 2019 (COVID-19) outbreak, significant advancements has been made in research, from limited knowledge about the disease to the development of a vaccine. Although the severity of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) appears to be decreasing and the threat of COVID-19 is waning, there have been widespread concerns about persistent symptoms or sequelae experienced by some patients even after recovering from COVID-19. Traditional Chinese medicine (TCM) has shown favorable treatment outcomes during the onset of COVID-19, and extensive studies have been carried out to explore the efficacy of TCM interventions during the COVID-19 recovery period. The purpose of this review is to comprehensively analyze these studies and provide new insights for the prevention and treatment of the post-COVID-19 condition.


Subject(s)
COVID-19 , Drugs, Chinese Herbal , Humans , Medicine, Chinese Traditional , SARS-CoV-2 , Drugs, Chinese Herbal/therapeutic use , COVID-19 Drug Treatment
6.
J Dev Orig Health Dis ; 15: e2, 2024 Mar 07.
Article in English | MEDLINE | ID: mdl-38450456

ABSTRACT

With the advancement of medical technology, there are increasing opportunities for new-borns, infants, and pregnant women to be exposed to general anaesthesia. Propofol is commonly used for the induction of anaesthesia, maintenance of general intravenous anaesthesia and sedation of intensive-care children. Many previous studies have found that propofol has organ-protective effects, but growing evidence suggests that propofol interferes with brain development, affecting learning and cognitive function. The purpose of this review is to summarize the latest progress in understanding the neurotoxicity of propofol. Evidence from case studies and clinical studies suggests that propofol has neurotoxicity on the developing brain. We classify the findings on propofol-induced neurotoxicity based on its damage mechanism. We end by summarizing the current protective strategies against propofol neurotoxicity. Fully understanding the neurotoxic mechanisms of propofol can help us use it at a reasonable dosage, reduce its side effects, and increase patient safety.


Subject(s)
Anesthesia , Propofol , Pregnancy , Humans , Female , Child , Propofol/toxicity , Anesthetics, Intravenous/adverse effects , Brain , Cognition
7.
Glob Chang Biol ; 30(3): e17250, 2024 Mar.
Article in English | MEDLINE | ID: mdl-38500362

ABSTRACT

Nitrogen (N) deposition affects ecosystem functions crucial to human health and well-being. However, the consequences of this scenario for soil ecosystem multifunctionality (SMF) in forests are poorly understood. Here, we conducted a long-term field experiment in a temperate forest in China, where N deposition was simulated by adding N above and under the canopies. We discover that canopy N addition promotes SMF expression, whereas understory N addition suppresses it. SMF was regulated by fungal diversity in canopy N addition treatments, which is largely due to the strong resistance to soil acidification and efficient resource utilization characteristics of fungi. While in understory N addition treatments, SMF is regulated by bacterial diversity, which is mainly because of the strong resilience to disturbances and fast turnover of bacteria. Furthermore, rare microbial taxa may play a more important role in the maintenance of the SMF. This study provides the first evidence that N deposition enhanced SMF in temperate forests and enriches the knowledge on enhanced N deposition affecting forest ecosystems. Given the divergent results from two N addition approaches, an innovative perspective of canopy N addition on soil microbial diversity-multifunctionality relationships is crucial to policy-making for the conservation of soil microbial diversity and sustainable ecosystem management under enhanced N deposition. In future research, the consideration of canopy N processes is essential for more realistic assessments of the effects of atmospheric N deposition in forests.


Subject(s)
Ecosystem , Nitrogen , Humans , Nitrogen/analysis , Soil , Soil Microbiology , Forests , Bacteria/metabolism
8.
Chemphyschem ; 25(6): e202300835, 2024 Mar 15.
Article in English | MEDLINE | ID: mdl-38372432

ABSTRACT

With the popularity and development of electronic devices, the demand for lithium batteries is increasing, which also puts high demands on the energy density, cycle life and safety of lithium batteries. Gel electrolytes achieve both of these requirements by curing the electrolytes to reduce the interfacial side reactions of lithium metal batteries. The ionic conductivity of the gel electrolytes prepared by in situ curing reach 8.0×10-4  S cm-1 , and the ionic mobility number is 0.53. Meanwhile, the gel electrolytes maintain a stable electrochemical window of 1.0-5.0 V. Benefited with the interfacial regulation of PEGDA gel electrolytes, the gel lithium metal batteries show better cycling stability, and achieved 97 % capacity retention after 200 cycles (0.2 C) with a lower increasing rate of impedance.

9.
Eur J Med Chem ; 265: 116079, 2024 Feb 05.
Article in English | MEDLINE | ID: mdl-38150962

ABSTRACT

In this work, a series of novel coumarin-based derivatives were designed and synthesized as tubulin polymerization inhibitors targeting the colchicine binding site, and their antiproliferative activities against MGC-803, HCT-116 and KYSE30 cells were evaluated. Among them, the compound I-3 (MY-1442) bearing a 6-methoxy-1,2,3,4-tetrahydroquinoline group exhibited most potent inhibitory activities on MGC-803 (IC50 = 0.034 µM), HCT-116 (IC50 = 0.081 µM) and KYSE30 cells (IC50 = 0.19 µM). Further mechanism studies demonstrated that compound I-3 (MY-1442) could directly bind to the colchicine binding site of ß-tubulin to inhibit tubulin polymerization and microtubules at the cellular level. The results of molecular docking indicated there were well binding interactions between compound I-3 (MY-1442) and the colchicine binding site of ß-tubulin. Compound I-3 (MY-1442) also exhibited effective anti-proliferation, pro-apoptosis, and anti-migration abilities against gastric cancer cells MGC-803. Additionally, compound I-3 (MY-1442) could regulate the expression of cell cycle- and apoptosis-related proteins. Importantly, compound I-3 (MY-1442) could significantly inhibit tumor growth in the MGC-803 xenograft tumor model with a TGI rate of 65.5 % at 30 mg/kg/day. Taken together, this work suggested that the coumarin skeleton exhibited great potential to be a key pharmacophore of tubulin polymerization inhibitors for the discovery of anticancer agents.


Subject(s)
Antineoplastic Agents , Stomach Neoplasms , Humans , Colchicine/pharmacology , Tubulin/metabolism , Tubulin Modulators/chemistry , Molecular Docking Simulation , Stomach Neoplasms/drug therapy , Polymerization , Cell Proliferation , Binding Sites , Coumarins/pharmacology , Antineoplastic Agents/pharmacology , Antineoplastic Agents/chemistry , Drug Screening Assays, Antitumor
10.
J Cancer ; 14(18): 3496-3507, 2023.
Article in English | MEDLINE | ID: mdl-38021164

ABSTRACT

Background: Neuroblastoma (NB) is a cancer that arises from neural-crest-derived sympathoadrenal lineage. Less is known about the pathogenesis and molecular characteristics of MYCN non-amplified (MYCN-NA) NB. Methods: We constructed a signature model targeting mucin family according to RNA sequencing data from GSE49710 dataset, and validated the prognostic performance. We also analyzed the gene expression matrix using DESeq2 R packages to screen the most differential mucin in high-risk NB samples. We further assessed its prognostic value, particularly in MYCN-NA NB samples. Moreover, we performed functional experiments to evaluate the impact of MUC15 overexpression on the migration of MYCN-NA NB cell lines. Results: The 8-mucin signature model showed good prognostic performance in the GSE49710 dataset. Among the mucin genes, MUC15 was significantly upregulated in the high-risk NB cohort and was associated with poor prognosis, especially in MYCN-NA NB samples. Furthermore, MUC15 overexpression and exogenous MUC15 protein enhanced the migration of MYCN-NA NB cell lines. Mechanistically, MUC15 promoted the phosphorylation of focal adhesion kinase (FAK) by inhibiting the expression of MYCT1, a target of c-Myc. Conclusions: Our findings suggested a potential network in controlling NB cell metastasis. Targeting MUC15 in MYCN-NA NB patients could be a promising therapeutic strategy.

11.
Article in English | MEDLINE | ID: mdl-38028893

ABSTRACT

Background: Hong Kong experienced four epidemic waves caused by the ancestral strain of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in 2020-2021 and a large Omicron wave in 2022. Few studies have assessed antibacterial prescribing for coronavirus disease 2019 (COVID-19) inpatients throughout the pandemic. Objectives: To describe inpatient antibacterial prescribing and explore factors associated with their prescription. Methods: Electronic health records of patients with COVID-19 admitted to public hospitals in Hong Kong from 21 January 2020 to 30 September 2022 were used to assess the prevalence and rates of inpatient antibacterial drug use (days of therapy/1,000 patient days [DOT/1,000 PD]). We used multivariable logistic regression to investigate potential associations between patients' baseline characteristics and disease severity and prescription of an antibacterial drug during hospital admission. Results: Among 65,810 inpatients with COVID-19, 54.0% were prescribed antibacterial drugs (550.5 DOT/1,000 PD). Compared to waves 1-2 (46.7%; 246.9 DOT/1,000 PD), the prescriptions were lowest during wave 4 (28.0%; 246.9; odds ratio (OR): 0.39, 95% CI: 0.31-0.49) and peaked in early wave 5 (64.6%; 661.2; 0.82, 0.65-1.03). Older age (≥80 years: OR 2.66, 95% CI, 2.49-2.85; 60-79 years: 1.59, 1.51-1.69, compared with 20-59 years), more severe disease (fatal: 3.64, 3.2-4.16; critical: 2.56, 2.14-3.06, compared with severe), and COVID-19 vaccine doses (two doses: 0.74, 0.69-0.78; three doses: 0.69, 0.64-0.74; four doses: 0.52, 0.44-0.62, compared with unvaccinated) were associated with inpatient antibacterial drug use. Conclusions: Antibacterial prescribing changed over time for hospitalized patients with confirmed COVID-19 and was potentially related to patients' demographics, medical conditions, and COVID-19 vaccination status as well as healthcare capacity during epidemic waves.

12.
Internet Interv ; 34: 100690, 2023 Dec.
Article in English | MEDLINE | ID: mdl-38023965

ABSTRACT

Purpose: This meta-analysis aims to evaluate the impact of Internet-based self-help interventions on the mental health of adolescents and college students. Methods: We conducted a systematic review of randomized controlled trials (RCTs) that investigated Internet-based self-help interventions aiming to mitigate mental health symptoms such as anxiety and depression, as well as managing high levels of stress, among adolescents and college students. Our search spanned databases including Web of Science, PubMed, Cochrane Library, and Embase, up until November 1st, 2022. It is essential to emphasize that our focus was the evaluation of symptoms (continuous outcomes), rather than the diagnosis of specific mental disorders. The meta-analysis was performed using the R version 4.3.1. The effect size measure was the standardized mean difference (SMD), and random-effects models were used to pool data from eligible RCTs. Subgroup analyses were carried out to examine variations in intervention effects based on factors such as sample type, intervention modality, guidance type, and intervention duration. Results: The meta-analysis was based on 25 comparisons involving a total of 4480 participants. In comparison to the control group (n = 2125), participants receiving interventions (n = 2355) reported significant reductions in symptoms of anxiety, depression, and stress, along with a significant improvement in quality of life. Specifically, for depression, we observed moderate intervention effects (SMD = -0.42, 95 % CI: -0.56, -0.27), and a similar pattern was seen for quality of life (SMD = 0.36, 95%CI: 0.22, 0.49). Small intervention effects were found for anxiety (SMD = -0.35, 95 % CI [-0.48, -0.22]) and stress (SMD = -0.35, 95 % CI [-0.51, -0.20]). Given significant heterogeneity, subgroup analyses were conducted for anxiety and depression, considering factors such as sample type, intervention method, and intervention duration. Notably, college students experienced more significant benefits in both anxiety and depression alleviation compared to adolescents. Longer interventions (>8 weeks) were particularly effective in reducing anxiety and depression. Additionally, third-wave cognitive-behavioral therapy (CBT) showed pronounced intervention effects in both outcome measures, while the presence of guidance did not notably influence results. Conclusion: This meta-analysis underscores the positive impact of Internet-based self-help programs in alleviating the symptoms of psychological disorders among adolescents and college students. However, it is crucial to acknowledge that the available evidence exhibits inconsistencies and limitations. Therefore, further research utilizing rigorous methodologies is necessary to verify and broaden the findings of this meta-analysis.

14.
Biotechnol Biofuels Bioprod ; 16(1): 161, 2023 Oct 27.
Article in English | MEDLINE | ID: mdl-37891680

ABSTRACT

BACKGROUND: The well-known industrial fungus Trichoderma reesei has an excellent capability of secreting a large amount of cellulases and xylanases. The induced expression of cellulase and xylanase genes is tightly controlled at the transcriptional level. However, compared to the intensive studies on the intricate regulatory mechanism of cellulase genes, efforts to understand how xylanase genes are regulated are relatively limited, which impedes the further improvement of xylanase production by T. reesei via rational strain engineering. RESULTS: To identify transcription factors involved in regulating xylanase gene expression in T. reesei, yeast one-hybrid screen was performed based on the promoters of two major extracellular xylanase genes xyn1 and xyn2. A putative transcription factor named XTR1 showing significant binding capability to the xyn1 promoter but not that of xyn2, was successfully isolated. Deletion of xtr1 significantly increased the transcriptional level of xyn1, but only exerted a minor promoting effect on that of xyn2. The xylanase activity was increased by ~ 50% with XTR1 elimination but the cellulase activity was hardly affected. Subcellular localization analysis of XTR1 fused to a green fluorescence protein demonstrated that XTR1 is a nuclear protein. Further analyses revealed the precise binding site of XTR1 and nucleotides critical for the binding within the xyn1 promoter. Moreover, competitive EMSAs indicated that XTR1 competes with the essential transactivator XYR1 for binding to the xyn1 promoter. CONCLUSIONS: XTR1 represents a new transcriptional repressor specific for controlling xylanase gene expression. Isolation and functional characterization of this new factor not only contribute to further understanding the stringent regulatory network of xylanase genes, but also provide important clues for boosting xylanase biosynthesis in T. reesei.

15.
Front Psychol ; 14: 1184985, 2023.
Article in English | MEDLINE | ID: mdl-37546475

ABSTRACT

Introduction: The current study aimed to explore the relationship between family function and adolescent altruistic behavior, as well as the mediating effects of self-affirmation and psychological resilience in this relationship. Methods: A survey was conducted on 972 high school students in Guangdong Province using the Family APGAR, GHQSense of Adequacy, Chinese version of Connor-Davidson Resilience Scale, and Altruistic Behavior Scale. Results: Results found that the score of psychological resilience of males was significantly higher than that of females, but the score of altruistic behavior was significantly lower than that of females. Family function had a positive predictive effect on altruistic behavior. Psychological resilience played a mediating role between family function and altruistic behavior. Self-affirmation and psychological resilience played chain mediating roles between family function and altruistic behavior. Discussion: This study indicated that family care is crucial for the development of adolescent altruistic behavior, and that it can promote the development of altruistic behavior through the enhancement of self-affirmation and psychological resilience.

16.
World J Gastrointest Surg ; 15(7): 1474-1484, 2023 Jul 27.
Article in English | MEDLINE | ID: mdl-37555116

ABSTRACT

BACKGROUND: Acupuncture promotes the recovery of gastrointestinal function and provides analgesia after major abdominal surgery. The effects of transcutaneous electrical acupoint stimulation (TEAS) remain unclear. AIM: To explore the potential effects of TEAS on the recovery of gastrointestinal function after gastrectomy and colorectal resection. METHODS: Patients scheduled for gastrectomy or colorectal resection were randomized at a 2:3:3:2 ratio to receive: (1) TEAS at maximum tolerable current for 30 min immediately prior to anesthesia induction and for the entire duration of surgery, plus two 30-min daily sessions for 3 consecutive days after surgery (perioperative TEAS group); (2) Preoperative and intraoperative TEAS only; (3) Preoperative and postoperative TEAS only; or (4) Sham stimulation. The primary outcome was the time from the end of surgery to the first bowel sound. RESULTS: In total, 441 patients were randomized; 405 patients (58.4 ± 10.2 years of age; 247 males) received the planned surgery. The time to the first bowel sounds did not differ among the four groups (P = 0.90; log-rank test). On postoperative day 1, the rest pain scores differed significantly among the four groups (P = 0.04; Kruskal-Wallis test). Post hoc comparison using the Bonferroni test showed lower pain scores in the perioperative TEAS group (1.4 ± 1.2) than in the sham stimulation group (1.7 ± 1.1; P = 0.04). Surgical complications did not differ among the four groups. CONCLUSION: TEAS provided analgesic effects in adult patients undergoing major abdominal surgery, and it can be added to clinical practice as a means of accelerating postoperative rehabilitation of these patients.

17.
J Agric Food Chem ; 71(31): 11993-12003, 2023 Aug 09.
Article in English | MEDLINE | ID: mdl-37523749

ABSTRACT

To achieve cost-effective production of lignocellulolytic enzymes for biorefinery processes, engineering transcription factors represents a powerful strategy to boost cellulase and xylanase in Trichoderma reesei. In this study, a novel mutation (R434L) in xylanase regulator 1 (Xyr1) was identified based on the yeast one-hybrid screening system. The point mutation was located in the middle homology region of Xyr1 with unclear functions, indicating a significant role for this domain in tuning Xyr1 transactivation. When constitutively expressed in T. reesei Δxyr1 (OEXR434L), Xyr1R434L led to highly improved production of both cellulases and xylanases on glucose compared with a strain similarly expressing Xyr1 (OEX). The respective 0.8- and 0.7-fold increases in extracellular pNPCase and xylanolytic activity were further verified to result from the greatly elevated transcription of major cellulase and xylanase genes in OEXR434L. Moreover, the saccharification efficiency of corn stover with OEXR434L enzyme cocktails was enhanced by 21% compared with that of OEX.


Subject(s)
Cellulase , Cellulases , Trichoderma , Cellulase/genetics , Cellulase/metabolism , Glucose , Promoter Regions, Genetic , Cellulases/genetics , Mutation , Trichoderma/metabolism , Gene Expression Regulation, Fungal , Fungal Proteins/genetics , Fungal Proteins/metabolism
18.
Eur J Med Chem ; 259: 115673, 2023 Nov 05.
Article in English | MEDLINE | ID: mdl-37487305

ABSTRACT

Histone deacetylases, as a new class of anticancer targets, could maintain homeostasis by catalyzing histone deacetylation and play important roles in regulating the expression of target genes. Due to the fact that simultaneous intervention with dual tumor related targets could improve treatment effects, researches on innovative design of dual-target drugs are underway. HDAC is known as a "sensitizer" for the synergistic effects with other anticancer-target drugs because of its flexible structure design. The synergistic effects of HDAC inhibitor and other target inhibitors usually show enhanced inhibitory effects on tumor cells, and also provide new strategies to overcome multidrug resistance. Many research groups have reported that simultaneously inhibiting HDAC and other targets, such as tubulin, EGFR, could enhance the therapeutic effects. The o-aminobenzamide group is often used as a ZBG group in the design of HDAC inhibitors with potent antitumor effects. Given the prolonged inhibitory effects and reduced toxic side effects of HDAC inhibitors using o-aminobenzamide as the ZBG group, the o-aminobenzamide group is expected to become a more promising alternative to hydroxamic acid. In fact, o-aminobenzamide-based dual inhibitors of HDAC with different chemical structures have been extensively prepared and reported with synergistic and enhanced anti-tumor effects. In this work, we first time reviewed the rational design, molecular docking, inhibitory activities and potential application of o-aminobenzamide-based HDAC inhibitors with dual targeting capabilities in cancer therapy, which might provide a reference for developing new and more effective anticancer drugs.


Subject(s)
Antineoplastic Agents , Neoplasms , Histone Deacetylase Inhibitors/chemistry , Molecular Docking Simulation , Cell Line, Tumor , Antineoplastic Agents/chemistry , Tubulin , Cell Proliferation , Neoplasms/drug therapy
19.
Ann Med Surg (Lond) ; 85(6): 2662-2676, 2023 Jun.
Article in English | MEDLINE | ID: mdl-37363456

ABSTRACT

Yiqi Tuomin Decoction (YTD), which originated from the theory of lung deficiency and cold in Chinese medicine, is a common Chinese herbal formula used against allergic rhinitis (AR). In our otolaryngology department, this prescription has been used to treat so many AR patients with lung-deficiency-related colds for nearly 30 years. However, the mechanism of its ingredient-target is still unclear. Based on our early experiments and clinical case studies, in this paper, we explore the mechanism of YTD systematically against AR using bioinformatic methods of network pharmacology and molecular docking. Methods: The Traditional Chinese Medicine Systems Pharmacology (TCMSP) database was used to screen the active ingredients and targets of YTD. The AR-related targets were retrieved from OMIM, GeneCards, TTD, DisGeNET, DrugBank databases, and PharmGKB. The Venn database was used to screen the potential core targets. After that, the STRING database was used to construct the protein-protein interaction (PPI) of the core targets and then visualize it by Cytoscape. The Gene Ontology (GO)-enriched processes and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways of the core targets were analyzed by the KOBAS-I database and Sangerbox. Molecular docking was used to assess interactions between potential targets and active ingredients. Results: A total of 169 active ingredients and 238 targets of YTD were predicted. YTD shared 115 common targets with AR from the Venn database. The GO-enriched processes and KEGG pathways indicate that genes involved in inflammation and oxidative stress, accompanying the MAPK signaling pathway, Th17 cell differentiation, IL-17 signaling pathway, and Th1 and Th2 cell differentiation, may play a mediated effect in YTD. The docking results showed good binding ability between the active ingredients and the selected targets. Conclusions: Our study systematically indicated the underlying mechanism of YTD against AR from the perspective of bioinformatics. By studying the active ingredients of YTD, we obtained molecular mechanisms and established a reliable method and molecular theoretical basis for the sensible development of Chinese medicine in the treatment of AR.

20.
Neurol Res ; 45(9): 858-866, 2023 Sep.
Article in English | MEDLINE | ID: mdl-37356109

ABSTRACT

OBJECTIVE: Glioma is a heterogeneous group of brain tumors that remains largely incurable. Constitutive photomorphogenic 1 (COP1) acts as an E3 ligase for tumor regulation. This study explored the mechanism of COP1 in glioma cell proliferation, invasion, and migration. METHODS: COP1 and discs large homolog 3 (DLG3) expressions in glioma cells were determined using RT-qPCR or Western blotting, followed by transfection of si-COP1 or si-DLG3 into LN229 cells. Glioma cell proliferation, invasion, and migration were measured using CCK-8, EdU staining, and Transwell assays. The binding of COP1 and DLG3 was verified using co-immunoprecipitation. The ubiquitination level of DLG3 protein was tested after MG132 treatment. Functional rescue experiments were performed to validate the role of DLG3 in the regulation of glioma cells by COP1. RESULTS: COP1 was highly expressed in glioma cells. COP1 silencing repressed glioma cell proliferation, invasion, and migration. COP1 bound to DLG3 protein and enhanced the ubiquitination of DLG3. DLG3 silencing reversed the inhibitory effect of COP1 silencing on glioma cell proliferation, invasion, and migration. CONCLUSION: COP1 facilitated the proliferation, invasion, and migration of glioma cells by ubiquitination of DLG3 protein.


Subject(s)
Brain Neoplasms , Glioma , Humans , Ubiquitination , Glioma/pathology , Ubiquitin-Protein Ligases/genetics , Brain Neoplasms/pathology , Cell Line, Tumor , Cell Proliferation , Nuclear Proteins/metabolism , Transcription Factors/metabolism
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