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1.
Front Pharmacol ; 15: 1408993, 2024.
Article in English | MEDLINE | ID: mdl-38939839

ABSTRACT

Ginsenosides, the primary bioactive ingredients derived from the root of Panax ginseng, are eagerly in demand for tumor patients as a complementary and alternative drug. Ginsenosides have increasingly become a "hot topic" in recent years due to their multifunctional role in treating colorectal cancer (CRC) and regulating tumor microenvironment (TME). Emerging experimental research on ginsenosides in the treatment and immune regulation of CRC has been published, while no review sums up its specific role in the CRC microenvironment. Therefore, this paper systematically introduces how ginsenosides affect the TME, specifically by enhancing immune response, inhibiting the activation of stromal cells, and altering the hallmarks of CRC cells. In addition, we discuss their impact on the physicochemical properties of the tumor microenvironment. Furthermore, we discuss the application of ginsenosides in clinical treatment as their efficacy in enhancing tumor patient immunity and prolonging survival. The future perspectives of ginsenoside as a complementary and alternative drug of CRC are also provided. This review hopes to open up a new horizon for the cancer treatment of Traditional Chinese Medicine monomers.

2.
Chin J Integr Med ; 2024 Jun 08.
Article in English | MEDLINE | ID: mdl-38850480

ABSTRACT

OBJECTIVE: To analyze Chinese medicine (CM) prescriptions for gastroesophageal reflux disease (GERD), we model topics on GERD-related classical CM literature, providing insights into the potential treatment. METHODS: Clinical guidelines were used to identify symptom terms for GERD, and CM literature from the database "Imedbooks" was retrieved for related prescriptions and their corresponding sources, indications, and other information. BERTopic was applied to identify the main topics and visualize the data. RESULTS: A total of 36,207 entries are queried and 1,938 valid entries were acquired after manually filtering. Eight topics were identified by BERTopic, including digestion function abate, stomach flu, respiratory-related symptoms, gastric dysfunction, regurgitation and gastrointestinal dysfunction in pediatric patients, vomiting, stroke and alcohol accumulation are associated with the risk of GERD, vomiting and its causes, regurgitation, epigastric pain, and symptoms of heartburn. CONCLUSIONS: Topic modeling provides an unbiased analysis of classical CM literature on GERD in a time-efficient and scale-efficient manner. Based on this analysis, we present a range of treatment options for relieving symptoms, including herbal remedies and non-pharmacological interventions such as acupuncture and dietary therapy.

3.
Adv Mater ; : e2311489, 2024 May 02.
Article in English | MEDLINE | ID: mdl-38696759

ABSTRACT

Slippery surfaces, which originate in nature with special wettability, have attracted considerable attention in both fundamental research and practical applications in a variety of fields due to their unique characteristics of superlow liquid friction and adhesion. Although research on bioinspired slippery surfaces is still in its infancy, it is a rapidly growing and enormously promising field. Herein, a systematic review of recent progress in bioinspired slippery surfaces, beginning with a brief introduction of several typical creatures with slippery property in nature, is presented. Subsequently,this review gives a detailed discussion on the basic concepts of the wetting, friction, and drag from micro- and macro-aspects and focuses on the underlying slippery mechanism. Next, the state-of-the-art developments in three categories of slippery surfaces of air-trapped, liquid-infused, and liquid-like slippery surfaces, including materials, design principles, and preparation methods, are summarized and the emerging applications are highlighted. Finally, the current challenges and future prospects of various slippery surfaces are addressed.

4.
Immunopharmacol Immunotoxicol ; 45(2): 213-223, 2023 Apr.
Article in English | MEDLINE | ID: mdl-36218392

ABSTRACT

BACKGROUND: Secoeudesma sesquiterpenes lactone A (SESLA) is a sesquiterpene derived from Inula japonica Thunb. and is known to possess many pharmacological properties, e.g. anti-tumor and anti-inflammatory activities. However, the immunomodulatory role of SESLA in gram-positive (G+) bacterial infection is not clear. MATERIALS AND METHODS: To set up a G+ bacterial infection model in vitro, we carried out a bacterial mimic (PGN or Pam3CSK4) or Methicillin-resistant Staphylococcus aureus (MRSA) stimulated experiment using macrophages or dendritic cells (DCs). ELISA and qPCR were performed to measure the expression of inflammatory cytokines. Flow cytometry was used to detect the expression of MHC II and co-stimulatory molecules on the surface of DCs. The network pharmacology was used to identify the molecular mechanism and potential targets of SESLA that are predicted to be involved in the MRSA-elicited inflammation. Western blot and dual luciferase reporter assay were adopted to certify possible molecular mechanism of SESLA. RESULTS: This study demonstrated that SESLA treatment significantly reduced the levels of inflammatory cytokines stimulated by PGN, Pam3CSK4 or even MRSA in vitro, and it also reduced PGN-induced expression of MHC II and co-stimulatory molecules on the surface of DCs. Mechanistically, the inhibition of IκBα phosphorylation and the suppression of T cells activation could account for its anti-inflammatory activity. CONCLUSION: The present study validated the notable anti-inflammatory activity of SESLA and discovered its previously uncharacterized immunoregulatory role and the underlying mechanism in G+ bacterial infections. Overall, SESLA has a potential to be an antibiotic adjuvant for the treatment of G+ bacterial infections.


Subject(s)
Methicillin-Resistant Staphylococcus aureus , Staphylococcal Infections , Humans , Methicillin-Resistant Staphylococcus aureus/metabolism , Macrophages/metabolism , Cytokines/metabolism , Anti-Inflammatory Agents/pharmacology , Anti-Inflammatory Agents/therapeutic use , Dendritic Cells/metabolism , Staphylococcal Infections/drug therapy , Staphylococcal Infections/metabolism , Staphylococcal Infections/microbiology
5.
Front Public Health ; 10: 1015811, 2022.
Article in English | MEDLINE | ID: mdl-36353283

ABSTRACT

Objective: To evaluate determinants of prolonged viral RNA shedding in hospitalized patients with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) Omicron variant infection. Materials and methods: Hospitalized patients tested SARS-CoV-2 positive by nasopharyngeal real-time reverse transcriptase-polymerase chain reaction (RT-PCR) were included in the single-center, retrospective study. Patients were divided into 2 groups according to the timing of viral clearance (≤ 8 days, "early clearance" and ≥15 days, "late clearance"). Results: 4,084 patients were included in the study (1,023 late clearance, 3,061 early clearance), with median age of 50 years and a higher proportion (61.4%) of male. Univariate analyses showed that comorbidities (including hypertension, diabetes, and coronary heart disease), receiving vaccine, the number of vaccinations, cycle threshold (Ct) open reading frame 1ab (ORF 1ab), and nucleocapsid protein (N) gene values on admission were associated with late viral clearance. In the multivariable analysis, the number of vaccinations (P = 0.010) and Ct ORF 1ab gene (P < 0.001) values on admission were significantly associated with late viral clearance. Generalized Estimating Equations (GEE) analysis showed that the Ct value of ORF 1ab gene and N gene remained unchanged within 3 days, and showed progressively higher values with increasing days during late viral RNA clearance. Conclusion: The number of vaccinations and Ct values of ORF 1ab gene were independently associated with a prolonged SARS-CoV-2 RNA shedding.


Subject(s)
COVID-19 , SARS-CoV-2 , Humans , Male , Middle Aged , SARS-CoV-2/genetics , Virus Shedding , Reverse Transcriptase Polymerase Chain Reaction , RNA, Viral/analysis , Retrospective Studies , COVID-19/epidemiology , China/epidemiology
6.
Toxicol Res (Camb) ; 11(3): 498-510, 2022 Jun.
Article in English | MEDLINE | ID: mdl-35782639

ABSTRACT

Dezocine, a dual agonist and antagonist of the µ-opioid receptor and κ-opioid receptor, is widely used as an analgesic in China. At present, there are few studies on anti-tumor effects of dezocine, most of which are used to treat cancer pain. However, it has recently been reported that dezocine can induce apoptosis of triple negative breast cancer cells. Dezocine may have some anti-tumor activity, but the effect and potential mechanism of dezocine in the treatment of other types of cancer remain to be fully studied. The purpose of the present study was to investigate the effect of dezocine on human Hela cervical carcinoma cells, and to elucidate the underlying molecular mechanisms. We performed CCK-8 assays, clone formation assays, xenograft, flow cytometry analysis, western blot and RNA-seq analysis to evaluate the effects of dezocine on Hela cells. In addition, the role of endoplasmic reticulum (ER) stress in dezocine-induced apoptosis was investigated using qPCR and western blot analysis. Dezocine inhibited Hela cell viability in dose-dependent and time-dependent manners, and notably did not achieve this effect by targeting the opioid receptors. Further mechanistic studies demonstrated that dezocine activated ER stress by upregulating the expression of GRP78, IRE1 and p-JNK, and that dezocine-induced apoptosis was attenuated when the ER stress pathway was blocked. Our results provide a foundation to support the redefinition of dezocine as a novel, adjuvant treatment for patients with cervical cancer, although further research will be required to support its application in clinical practice.

7.
J Clin Lab Anal ; 36(2): e24194, 2022 Feb.
Article in English | MEDLINE | ID: mdl-35028969

ABSTRACT

BACKGROUND: Nasopharyngeal carcinoma is cancer with unique epidemiological characteristics, showing obvious ethnicity, gender, and geographical prevalence. More and more evidence shows that microRNAs are stable in serum and are specific to different tumor types. Therefore, miRNA is a new non-invasive biomarker for cancer detection. METHODS: The experiment is divided into three stages, namely, the screening stage, the training stage, and the verification stage. We took 54 patients with nasopharyngeal carcinoma and 108 healthy controls as the research objects. We use the receiver-operating characteristic (ROC) curve and area under the ROC curve (AUC) to evaluate the diagnostic value of miRNA. Finally, a three-miRNA panel with high diagnostic efficiency was constructed. In addition, we conducted biological information analysis of these miRNAs to explore their functions. RESULTS: In NPC patients, the expression of five serum miRNAs (miR-29c-3p, miR-143-5p, miR-150-5p, miR-145-3p, and miR-205-5p) is significantly dysregulated. Among them, the diagnostic value of these three miRNAs (miR-29c-3p, AUC = 0.702; miR-143-5p, AUC = 0.733; and miR-205-5p, AUC = 787) is more prominent. The diagnostic panel constructed by them has a higher diagnostic value (AUC = 0.902). Through the analysis of the TCGA data set, the target gene of the three-miRNA panel may be KLF7, NRG1, SH3BGRL2, and SYNPO2. CONCLUSION: The three-miRNA panel (miR-29c-3p, miR-143-5p, and miR-205-5p) may become a novel non-invasive biological marker for nasopharyngeal cancer screening.


Subject(s)
Biomarkers, Tumor/blood , Circulating MicroRNA/blood , Nasopharyngeal Carcinoma/genetics , Adult , Early Detection of Cancer/methods , Female , Gene Expression Profiling , Humans , Male , Middle Aged , Nasopharyngeal Carcinoma/blood , Nasopharyngeal Carcinoma/diagnosis , ROC Curve , Sensitivity and Specificity
8.
Oncol Lett ; 23(1): 20, 2022 Jan.
Article in English | MEDLINE | ID: mdl-34858524

ABSTRACT

Cordycepin is an extract from the Cordyceps genus of ascomycete fungi. In the present study, the anticancer potential of cordycepin against nasopharyngeal carcinoma (NPC), and the potential underlying mechanisms, were investigated. Using Cell Counting Kit 8, wound-healing and Transwell assays, cordycepin was found to reduce the viability and inhibit the migration of C666-1 cells in a dose-dependent manner. In addition, in colony formation assays, co-treatment with cordycepin and cisplatin inhibited the proliferation of C666-1 cells. Furthermore, RNA sequencing analysis identified 72 significantly differentially expressed genes and different signaling pathways that may be regulated by cordycepin. After treatment with cordycepin, the expression levels of ERK1/2, phosphorylated ERK1/2 and ß-catenin were significantly downregulated. Therefore, cordycepin may be a novel candidate for NPC treatment or a co-treatment candidate with cisplatin in chemotherapy.

9.
Bioengineered ; 12(2): 10608-10623, 2021 12.
Article in English | MEDLINE | ID: mdl-34747306

ABSTRACT

Dexmedetomidine (DEX) has been reported to attenuate cecal ligation perforation (CLP)-stimulated acute lung injury (ALI) by downregulating HMGB1 and RAGE. This study aimed to further investigate the specific mechanisms of RAGE and its potential-related mechanisms of DEX on ALI models in vitro and in vivo. The in vitro and in vivo ALI models were established by lipopolysaccharide treatment in MLE-12 cells and CLP in mice, respectively. The effect of DEX on pathological alteration was investigated by HE staining. Thereafter, the myeloperoxidase (MPO) activity and inflammatory cytokine levels were respectively detected to assess the lung injury of mice using commercial kits. The expression levels of HMGB1, RAGE, NF-κB, and pyroptosis-related molecules were detected by RT-qPCR and Western blot. HE staining showed that lung injury, increased inflammatory cell infiltration, and lung permeability was found in the ALI mice, and DEX treatment significantly attenuated lung tissue damage induced by CLP. The MPO activity and inflammatory cytokines (TNF-α, IL-1ß, and NLRP3) levels were also significantly reduced after DEX treatment compared with those in the ALI mice. Moreover, DEX activated the HMGB1/RAGE/NF-κB pathway and upregulated the pyroptosis-related proteins. However, the protective DEX effect was impaired by RAGE overexpression in ALI mice and MLE-12 cells. Additionally, DEX treatment significantly suppressed HMGB1 translocation from the nucleus region to the cytoplasm, and this effect was reversed by RAGE overexpression. These findings suggested that DEX may be a useful ALI treatment, and the protective effects on ALI mice may be through the inhibition of HMGB1/RAGE/NF-κB pathway and cell pyroptosis.


Subject(s)
Acute Lung Injury/drug therapy , Acute Lung Injury/etiology , Cecum/pathology , Dexmedetomidine/therapeutic use , HMGB1 Protein/metabolism , Protective Agents/therapeutic use , Pyroptosis , Receptor for Advanced Glycation End Products/metabolism , Animals , Cecum/drug effects , Cell Line , Cell Nucleus/drug effects , Cell Nucleus/metabolism , Cytokines/metabolism , Dexmedetomidine/pharmacology , Disease Models, Animal , Inflammation Mediators/metabolism , Lentivirus , Ligation , Lung/pathology , Male , Mice, Inbred C57BL , Protective Agents/pharmacology , Protein Transport/drug effects , Pyroptosis/drug effects , RNA, Messenger/genetics , RNA, Messenger/metabolism , Receptor for Advanced Glycation End Products/genetics , Signal Transduction/drug effects
10.
Open Med (Wars) ; 16(1): 1061-1069, 2021.
Article in English | MEDLINE | ID: mdl-34307888

ABSTRACT

Nasopharyngeal carcinoma (NPC) is characterized by high morbidity and morality, especially in Southern China. Transcription factors intensively participate in the initiation and development of NPC. This study aimed to investigate the roles of Src-1 in NPC. mRNA level was determined by qRT-PCR. Western blot was carried out for the protein level. CCK-8 assay was performed to determine cell viability, colony formation for NPC cell proliferation, and transwell for cell migration and invasion ability. The results showed Steroid receptor coactivator 1 (Src-1) was overexpressed in SNE-2 and 6-10B. The expression of Src-1 and SP2 was in positive correlation. Overexpression of Src-1 promoted the cell viability, colony formation, and epithelial-mesenchymal transition (EMT), manifested by the increase of migration and invasion ability, while knockdown of Src-1 exerted opposite effects. Additionally, knockdown or overexpression of SP2 reversed the effects of overexpressed or downregulated Src-1, which was reversed by the depletion of SP2. Moreover, Src-1 interacted with SP2 to regulate EMT-related genes such as E-cad, N-cad, Vimentin, and ZEB1, and proliferation- and apoptosis-related genes, such as bax, cytochrome c, and cleaved caspase3 and bcl-2. Thus, blocking the interaction between Src-1 and SP2 may be a therapeutic target for inhibiting the metastasis of NPC.

11.
Neural Plast ; 2021: 5528434, 2021.
Article in English | MEDLINE | ID: mdl-33976695

ABSTRACT

Background: Approximately 70% of congenital deafness is attributable to genetic causes. Incidence of congenital deafness is known to be higher in families with consanguineous marriage. In this study, we investigated the genetic causes in three consanguineous Pakistani families segregating with prelingual, severe-to-profound deafness. Results: Through targeted next-generation sequencing of 414 genes known to be associated with deafness, homozygous variants c.536del (p. Leu180Serfs∗20) in TECTA, c.3719 G>A (p. Arg1240Gln) in MYO7A, and c.482+1986_1988del in HGF were identified as the pathogenic causes of enrolled families. Interestingly, in one large consanguineous family, an additional c.706G>A (p. Glu236Lys) variant in the X-linked POU3F4 gene was also identified in multiple affected family members causing deafness. Genotype-phenotype cosegregation was confirmed in all participating family members by Sanger sequencing. Conclusions: Our results showed that the genetic causes of deafness are highly heterogeneous. Even within a single family, the affected members with apparently indistinguishable clinical phenotypes may have different pathogenic variants.


Subject(s)
Deafness/genetics , Extracellular Matrix Proteins/genetics , Hepatocyte Growth Factor/genetics , High-Throughput Nucleotide Sequencing/methods , Myosin VIIa/genetics , POU Domain Factors/genetics , Adult , Aged , Consanguinity , Female , GPI-Linked Proteins/genetics , Genes, X-Linked/genetics , Genotype , Humans , Male , Middle Aged , Pakistan , Pedigree , Phenotype
12.
Exp Ther Med ; 21(4): 315, 2021 Apr.
Article in English | MEDLINE | ID: mdl-33717258

ABSTRACT

The aim of the present study was to induce chronic atrophic gastritis (CAG) with intestinal metaplasia (IM) in rats by administering saturated salt and methyl-N'-nitro-N-nitrosoguanidine (MNNG) via oral gavage. Changes in gastric mucosal blood microcirculation and activation of the cyclo-oxygenase-2 (COX-2)/hypoxia inducible factor-1α (HIF-1α)/vascular endothelial growth factor (VEGF) signaling pathway during CAG and IM development were investigated. After administering saturated salt and MNNG for 25 weeks, mild atrophy was detected in the stomach of model rats using hematoxylin and eosin staining. CAG with IM was successfully induced in the gastric mucosa of the model rats after 35 weeks. Gastric mucosal blood flow was decreased in comparison with controls as early as 15 weeks after treatment to induce CAG and the mRNA expression levels of COX-2, HIF-1α, vascular endothelial growth factor receptor (VEGFR)1 and VEGFR2 were increased in comparison with untreated rats as early as 25 weeks after treatment. HIF-1α, COX-2 and VEGFR2 expression levels were increased as early as 25 weeks after CAG induction treatment when compared to controls and HIF-1α, COX-2, VEGFR1 and VEGFR2 expression levels were significantly increased after 35 weeks. These findings indicated that administering saturated salt and MNNG by gavage for 35 weeks successfully induced CAG and IM in rats. Furthermore, the microcirculation was disturbed before activation of the COX-2/HIF-1α/VEGF signaling pathway.

13.
Biomed Res Int ; 2021: 8890176, 2021.
Article in English | MEDLINE | ID: mdl-33564686

ABSTRACT

BACKGROUND: Nasopharyngeal carcinoma (NPC) is a rare but highly aggressive tumor that is predominantly encountered in Southeast Asia and China in particular. Aside from radiotherapy, no effective therapy that specifically treats NPC is available, including targeted drugs. Finding more sensitive biomarkers is important for new drug discovery and for evaluating patient prognosis. METHODS: mRNA expression datasets from the Gene Expression Omnibus database (GSE53819, GSE64634, and GSE40290) were selected. After all samples in each dataset were subjected to quality control using principal component analyses, the qualified samples were used for additional analyses. The genes that were significantly expressed in each dataset were intersected to identify the most significant of these. Gene functional enrichment analyses were performed on these genes, using Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes analyses. The protein-protein interaction network of selected genes was analyzed using the Search Tool for the Retrieval of Interacting Genes database. Significantly, differentially expressed genes were further verified with two RNA-seq datasets (GSE68799 and GSE12452), as well as in clinical samples. RESULTS: In all, 34 (8 upregulated genes and 26 downregulated) genes were identified as significantly differentially expressed. The immune response and the regulation of cell proliferation were the most enriched biological GO terms. Using reverse transcription quantitative real-time PCR (RT-qPCR), the genes MMP1, AQP9, and TNFAIP6 were detected to be upregulated, and FAM3D, CR2, and LTF were downregulated in NPC tissue samples. CONCLUSION: This study provides information on the genes that may be involved in the development of NPC and suggests possible druggable targets and biomarkers for diagnosing and evaluating the prognosis of NPC.


Subject(s)
Gene Expression Profiling/trends , Nasopharyngeal Carcinoma/genetics , Neoplasm Proteins/genetics , Transcriptome/genetics , Computational Biology , Disease-Free Survival , Female , Gene Expression Regulation, Neoplastic/genetics , Humans , Male , MicroRNAs , Nasopharyngeal Carcinoma/pathology , Prognosis , Protein Interaction Maps/genetics
14.
Auris Nasus Larynx ; 48(4): 723-730, 2021 Aug.
Article in English | MEDLINE | ID: mdl-33358379

ABSTRACT

OBJECTIVE: It remains elusive which factors may influence the morbidity and mortality of lung metastasis (LM) in Laryngeal Squamous Cell Carcinoma (LSCC) patients. The aim of the present study was to investigate factors influencing LM and the survival outcomes of LSCC patients with LM. METHODS: We identified 10,935 patients with LSCC from 2010 to 2014 using the Surveillance, Epidemiology and End Results database. Multivariate logistic regression analysis was used to determine the factors associated with the presence of LM. Multivariate cox regression analysis was used to identify covariates associated with increased all-cause mortality in patients with LM. RESULTS: Among 10,935 patients with LSCC, 232 (2.12%) patients had LM. The median survival time of patients with LM was 8 months, and 8.37% of patients survived after 3 years. Patients with age ≥ 60 years old, unmarried status, supraglottis, overlapping lesion of larynx, subglottis, pathological grade III, T4 stage, N1 stage, N2 stage, N3 stage and bone, brain or liver metastases were more likely to have LM. Survival analysis showed that chemotherapy and radiotherapy suggested better survival of LSCC patients with LM while pathological grade IV was associated with an increased all-cause mortality. CONCLUSION: The incidence of LSCC patients with LM varied by age, married status, and tumor subtypes. LSCC patients with LM had poor survival, and only 8.37% of patients survived after 3 years. However, chemotherapy and radiotherapy were found as independent favorable prognostic factors for survival.


Subject(s)
Carcinoma, Squamous Cell/secondary , Laryngeal Neoplasms/pathology , Lung Neoplasms/secondary , Age Distribution , Aged , Carcinoma, Squamous Cell/mortality , Carcinoma, Squamous Cell/pathology , China/epidemiology , Female , Humans , Incidence , Laryngeal Neoplasms/mortality , Logistic Models , Lung Neoplasms/mortality , Lung Neoplasms/pathology , Male , Marital Status , Middle Aged , Neoplasm Staging , Prognosis , Proportional Hazards Models , Risk Factors , SEER Program , Survival Analysis
15.
Appl Opt ; 59(22): 6505-6516, 2020 Aug 01.
Article in English | MEDLINE | ID: mdl-32749350

ABSTRACT

The next generation of optical telescopes will provide high-resolution imaging of celestial objects by using the aperture synthesis technique. To preserve the quality of the image, fast corrections of the pistons among subapertures have to be applied, namely, the co-phasing of the array. The image-based co-phasing method via an optimization procedure has been newly developed. Despite simplicity and strong commonality, when dealing with large piston errors, this correction method is also faced with a problem in which the metric function easily falls into the local convergence, especially in the case of broadband imaging with many subapertures. In this study, an improved stochastic parallel gradient descent (SPGD) algorithm based on heuristic search is proposed for co-phasing, termed the metaheuristic SPGD algorithm. The heuristic research scheme assists the original SPGD algorithm in getting rid of local extrema. By iterations of this algorithm, the synthetic system can be co-phased without any additional instruments and operations. The effectiveness of the proposed algorithm is verified by means of simulation. Given the efficiency and superiority, it is expected that the method proposed in this study may find wide applications in multi-aperture imaging.

16.
Theranostics ; 10(17): 7906-7920, 2020.
Article in English | MEDLINE | ID: mdl-32685028

ABSTRACT

Background: Capsaicin is an active compound found in plants of the Capsicum genus; it has a range of therapeutic benefits, including anti-tumor effects. Here we aimed to delineate the inhibitory effects of capsaicin on nasopharyngeal carcinoma (NPC). Methods: The anti-cancer effects of capsaicin were confirmed in NPC cell lines and xenograft mouse models, using CCK-8, clonogenic, wound-healing, transwell migration and invasion assays. Co-immunoprecipitation, western blotting and pull-down assays were used to determine the effects of capsaicin on the MKK3-p38 axis. Cell proliferation and EMT marker expression were monitored in MKK3 knockdown (KD) or over-expression NPC cell lines treated with or without capsaicin. Finally, immunohistochemistry was performed on NPC specimens from NPC patients (n = 132) and the clinical relevance was analyzed. Results: Capsaicin inhibited cell proliferation, mobility and promoted apoptosis in NPC cells. Then we found that capsaicin directly targets p38 for dephosphorylation. As such, MKK3-induced p38 activation was inhibited by capsaicin. Furthermore, we found that capsaicin-induced inhibition of cell motility was mediated by fucokinase. Xenograft models demonstrated the inhibitory effects of capsaicin treatment on NPC tumor growth in vivo, and analysis of clinical NPC samples confirmed that MKK3 phosphorylation was associated with NPC tumor growth and lymphoid node metastasis. Conclusions: The MKK3-p38 axis represents a potential therapeutic target for capsaicin. MKK3 phosphorylation might serve as a biomarker to identify NPC patients most likely to benefit from adjunctive capsaicin treatment.


Subject(s)
Capsaicin/pharmacology , MAP Kinase Kinase 3/metabolism , MAP Kinase Signaling System/drug effects , Nasopharyngeal Carcinoma/drug therapy , Nasopharyngeal Neoplasms/drug therapy , Animals , Capsaicin/therapeutic use , Cell Line, Tumor , Cell Movement/drug effects , Cell Proliferation/drug effects , Epithelial-Mesenchymal Transition/drug effects , Female , Gene Knockdown Techniques , HEK293 Cells , Humans , MAP Kinase Kinase 3/genetics , MAP Kinase Signaling System/genetics , Male , Mice , Middle Aged , Nasopharyngeal Carcinoma/pathology , Nasopharyngeal Neoplasms/pathology , Neoplasm Invasiveness/pathology , Neoplasm Invasiveness/prevention & control , Phosphorylation/drug effects , Phosphotransferases (Alcohol Group Acceptor)/genetics , Phosphotransferases (Alcohol Group Acceptor)/metabolism , Xenograft Model Antitumor Assays
17.
Mol Med Rep ; 22(2): 1567-1575, 2020 08.
Article in English | MEDLINE | ID: mdl-32626949

ABSTRACT

The study aimed to identify differentially expressed microRNAs (miRNAs/miRs) and explore the mechanisms governing impaired memory and learning ability in developing brains exposed to sevoflurane. A total of six 7­day­old male ICR mice were randomly assigned into the sevoflurane anesthesia group (treated with 2.4% sevoflurane) or control group (treated with normal saline solution at the same dose). After 14 days, the mice were subjected to a Morris water maze experiment. Then, the animals were sacrificed and hippocampus tissues were isolated. RNAs in hippocampus tissues were sequenced and the differential miRNA expression profiles were identified by a bioinformatics approach. The learning and memory function of mice were significantly affected by sevoflurane exposure. A total of 18 miRNAs were found to be significantly affected by sevoflurane administration. Their target genes clustered into different functional groups, such as 'dephosphorylation', 'vesicle localization' and the 'Wnt signaling pathway'. miR­101b­3p was closely related with 'chromatin binding' and 'protein serine/threonine kinase activity'. The most represented pathways for miRNAs included 'neuroactive ligand­receptor interaction' (miR­1187), 'long­term depression' (miR­425­5p), 'FoxO signaling pathway' (miR­425­5p) and the 'neurotrophin signaling pathway' (miR­467a­3p). miR­467a­3p (degree=89), miR­101b­3p (degree=59), and miR­1187 (degree=51) were the hub nodes in the miRNA regulatory network. The Wnt signaling pathway, miR­467a­3p, miR­1187 and miR­101b­3p may be therapeutic targets for preventing cognitive impairments induced by sevoflurane.


Subject(s)
Anesthetics, Inhalation/adverse effects , Hippocampus/drug effects , Memory Disorders/genetics , MicroRNAs/genetics , Sevoflurane/adverse effects , Animals , Animals, Newborn , Female , Male , Maze Learning/drug effects , Memory/drug effects , Mice , Mice, Inbred ICR , Pregnancy
18.
Opt Lett ; 45(7): 1790-1793, 2020 Apr 01.
Article in English | MEDLINE | ID: mdl-32236000

ABSTRACT

In this Letter, we report a segmented large-scaled lightweight diffractive telescope testbed newly built in our laboratory. The telescope, consisting of one 710-mm-diameter element in the center surrounded by eight 352-mm-diameter elements and a smaller eyepiece of achromatic lenses, can realize wide-band high-resolution imaging of 0.55-0.65 µm. The stitching errors are coarsely corrected by adjusting the motion stage mounted on each element. In particular, an optical synthesis system inserted behind the eyepiece is designed to compensate the residual tip-tilt-piston errors. We present the experimental imaging result of two stitched elements, which is the first successful experimental verification obtained by a practical segmented diffractive telescope to enhance the resolution. Moreover, spatial modulation diversity technology is used to restore the synthetic image so as to improve its quality and contrast.

19.
Am J Otolaryngol ; 41(4): 102452, 2020.
Article in English | MEDLINE | ID: mdl-32234257

ABSTRACT

PURPOSE: To review the prevalence and clinical characteristics of vestibular schwannoma (VS) in patients with sudden sensorineural hearing loss (SSNHL) in southern China. MATERIALS AND METHODS: This study examined the medical records and MRI findings of all the 1249 patients diagnosed with SSNHL between May 2009 and April 2019 in the Division of Otolaryngology at Peking University Shenzhen Hospital. RESULTS: Among the 1249 patients with SSNHL, VS was found in 14 (1.12%). Among 14 patients, 11 (78.6%) complained of tinnitus and 3 patients (21.4%) complained of dizziness as accompanying symptoms. There was one patient with SSNHL in right ear who had an incidental finding of VS in the contralateral ear. 2 patients (14.3%) had normal auditory brainstem response (ABR) test and 3 patients (21.4%) had hearing recovery. The size of tumors ranged from 6.1 mm to 24.2 mm, with 7 grade 1 tumors, 4 grade 2 tumors, and 3 grade 3 tumors. The total MRI screening cost was $130,857 and the average MRI cost for identifying a VS patient was $9346. CONCLUSION: The prevalence of VS among patients treated as SSNHL was 1.12%. Predicting the risk of VS in SSNHL by the audiogram patterns, pure tone audiometry or hearing recovery is not relivable. Compared with ABR, MRI is more suitable for the assessment of VS in patients with SSNHL in China.


Subject(s)
Hearing Loss, Sensorineural/diagnosis , Hearing Loss, Sudden/diagnosis , Neuroma, Acoustic/diagnosis , Neuroma, Acoustic/epidemiology , Adolescent , Adult , Aged , Aged, 80 and over , Child , China/epidemiology , Evoked Potentials, Auditory, Brain Stem , Female , Hearing Loss, Sensorineural/etiology , Hearing Loss, Sudden/etiology , Humans , Magnetic Resonance Imaging/economics , Male , Middle Aged , Neuroma, Acoustic/complications , Prevalence , Retrospective Studies , Time Factors , Young Adult
20.
Trials ; 21(1): 135, 2020 Feb 03.
Article in English | MEDLINE | ID: mdl-32014060

ABSTRACT

BACKGROUND: Diabetes mellitus is associated with risk of sudden sensorineural hearing loss (SSNHL). Systemic and intratympanic corticosteroids are the two primary treatments for SSNHL in patients with diabetes mellitus. The benefit of intratympanic compared to systemic treatment is the reduced systemic steroid exposure and associated systemic adverse effects. Intratympanic corticosteroid administration may have potential benefits over standard systemic therapies. METHODS/DESIGN: The proposed study is a prospective, randomized superiority trial. A total of 96 patients (48 in each group) will be randomized into the experimental or control group. Patients in the experimental group will receive four 1-mL doses of 40 mg/mL of methylprednisolone over a 1-week period, with a dose administered every 2 days via tympanic membrane injection into the middle ear. The control group will be administered intravenous methylprednisolone (1 mg/kg/day, maximal dose 60 mg/day) for 5 days. The primary outcome for this study is the change in hearing threshold from the first audiogram to the 30-day follow-up audiogram. Secondary outcome measures will include pure-tone average (PTA) at 90-day follow up, visual analog tinnitus scale, visual analog vertigo scale, visual analog aural fullness scale, fasting blood glucose and 2-h postprandial blood glucose during treatment, and the change in glycosylated hemoglobin (HbA1C) levels. Vital signs and otological physical examination will be performed at each follow-up visit. DISCUSSION: The efficacy and safety of intratympanic methylprednisolone compared to intravenous methylprednisolone will be investigated in patients with diabetes mellitus and SSNHL. This trial may provide strong evidence for the efficacy and safety of intratympanic corticosteroid treatment and important clinical information for the treatment of patients with diabetes mellitus and SSNHL. TRIAL REGISTRATION: ChiCTR, ChiCTR1800015954. Registered on 2 May 2018, Retrospectively registered, http://www.chictr.org.cn/showproj.aspx?proj=25326.


Subject(s)
Diabetes Complications , Glucocorticoids/administration & dosage , Hearing Loss, Sensorineural/drug therapy , Hearing Loss, Sensorineural/etiology , Hearing Loss, Sudden/drug therapy , Hearing Loss, Sudden/etiology , Injection, Intratympanic , Methylprednisolone/administration & dosage , Randomized Controlled Trials as Topic , Administration, Intravenous , Adolescent , Adult , Aged , Female , Follow-Up Studies , Glucocorticoids/adverse effects , Hearing/drug effects , Humans , Male , Methylprednisolone/adverse effects , Middle Aged , Prospective Studies , Treatment Outcome , Young Adult
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