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1.
Pak J Pharm Sci ; 37(1(Special)): 205-213, 2024 Jan.
Article in English | MEDLINE | ID: mdl-38747271

ABSTRACT

In this study, a sensitive high-performance liquid chromatography detector was established and validated for the simultaneous determination of geniposide, ellagic acid, piperine, costunolide and dehydrocostuslactone in Liuwei Muxiang Capsules. The analysis was achieved on CHANIN 100-5-C18-H column (5µm, 250 mm×4.6 mm) with the temperature of 30oC. Gradient elution was applied using 0.1% phosphoric acid solution-methanol-acetonitrile (50:50) as mobile phase at the flow rate of 1.0 mL/min. The determination was performed at the wavelength of 225 nm (detecting geniposide), 254 nm (detecting ellagic acid), 343 nm (detecting piperine) and 225 nm (detecting costunolide and dehydrocostuslactone) along with the sample volume of 10µL. The linear ranges of geniposide, ellagic acid, piperine, costunolide and dehydrocostuslactone demonstrated good linear relationships within their respective determination ranges. The average recoveries were 100.04%, 99.86%, 99.79%, 100.17% and 100.41%, respectively. RSD% was 1.3%, 1.2%, 1.2%, 1.2%, 1.5%, respectively. The developed method was proved to be simple, accurate and sensitive, which can provide a quantitative analysis method for the content determination of geniposide, ellagic acid, piperine, costunolide and dehydrocostuslactone in Liuwei Muxiang capsules.


Subject(s)
Alkaloids , Benzodioxoles , Capsules , Drugs, Chinese Herbal , Ellagic Acid , Iridoids , Lactones , Piperidines , Polyunsaturated Alkamides , Chromatography, High Pressure Liquid/methods , Benzodioxoles/analysis , Polyunsaturated Alkamides/analysis , Piperidines/analysis , Piperidines/chemistry , Alkaloids/analysis , Lactones/analysis , Drugs, Chinese Herbal/chemistry , Drugs, Chinese Herbal/analysis , Iridoids/analysis , Ellagic Acid/analysis , Reproducibility of Results , Sesquiterpenes/analysis
2.
Med Image Anal ; 96: 103202, 2024 May 15.
Article in English | MEDLINE | ID: mdl-38788326

ABSTRACT

Inadequate generality across different organs and tasks constrains the application of ultrasound (US) image analysis methods in smart healthcare. Building a universal US foundation model holds the potential to address these issues. Nevertheless, the development of such foundation models encounters intrinsic challenges in US analysis, i.e., insufficient databases, low quality, and ineffective features. In this paper, we present a universal US foundation model, named USFM, generalized to diverse tasks and organs towards label efficient US image analysis. First, a large-scale Multi-organ, Multi-center, and Multi-device US database was built, comprehensively containing over two million US images. Organ-balanced sampling was employed for unbiased learning. Then, USFM is self-supervised pre-trained on the sufficient US database. To extract the effective features from low-quality US images, we proposed a spatial-frequency dual masked image modeling method. A productive spatial noise addition-recovery approach was designed to learn meaningful US information robustly, while a novel frequency band-stop masking learning approach was also employed to extract complex, implicit grayscale distribution and textural variations. Extensive experiments were conducted on the various tasks of segmentation, classification, and image enhancement from diverse organs and diseases. Comparisons with representative US image analysis models illustrate the universality and effectiveness of USFM. The label efficiency experiments suggest the USFM obtains robust performance with only 20% annotation, laying the groundwork for the rapid development of US models in clinical practices.

3.
Circ Arrhythm Electrophysiol ; 17(5): e012513, 2024 May.
Article in English | MEDLINE | ID: mdl-38690657

ABSTRACT

BACKGROUND: The anatomy of myocardial fibers around the right cardiac veins (RCVs) and their roles in accessory pathways (APs) are rarely reported. METHODS: Six RCV-APs were identified from 566 patients with right-sided APs. Mapping of retrograde atrial activation was performed using CARTO 3 system under orthodromic tachycardia or right ventricular pacing. Venography of RCVs was acquired at the earliest retrograde atrial activation. RESULTS: Patients enrolled had a median age of 30 (11-51) years, 5 of them were male. Venography of RCVs could be classified into 3 distinct patterns based on the identified ventricular branches, right marginal vein only (type I; n=3), both right marginal vein and anterior cardiac veins (type II; n=2), and anterior cardiac vein only (type III; n=1). Patients with type I venography had rS QRS pattern in lead V1, negative delta wave in lead III and negative or isoelectric delta wave in lead aVF. However, patients with type II and III venography had QS QRS patterns in lead V1 and variable patterns of delta wave in inferior leads. Earliest retrograde atrial activation was found at a median of 16.75 (14.60-20.00) mm away from the tricuspid annulus, all with A larger than V. At the earliest retrograde atrial activation, far-field ventricular electrogram was found 30 ms later than QRS onset in 1 patient under sinus rhythm. AP conduction was eliminated by mechanical pressure in 2 and by radiofrequency ablation in 4 at the ostium of the veins colocalizing with the earliest retrograde activation of the right atrium. No recurrence was observed during 36 (10-60) months follow-up. CONCLUSIONS: The RCV-AP is a rare form of right-sided APs characterized by atrial insertions distant from the annulus. ECG-speculated ventricular insertion sites conformed to the location of identified RCVs.


Subject(s)
Accessory Atrioventricular Bundle , Catheter Ablation , Phlebography , Humans , Male , Adult , Female , Middle Aged , Accessory Atrioventricular Bundle/physiopathology , Accessory Atrioventricular Bundle/surgery , Adolescent , Young Adult , Child , Electrophysiologic Techniques, Cardiac , Coronary Vessels/physiopathology , Coronary Vessels/diagnostic imaging , Action Potentials , Heart Rate , Cardiac Pacing, Artificial
4.
Biochim Biophys Acta Mol Basis Dis ; 1870(5): 167208, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38701956

ABSTRACT

OBJECTIVE: This study aims to investigate the cardiac protective effects and molecular mechanisms of electroacupuncture (EA) pre-treatment in lipopolysaccharide (LPS)-Induced Cardiomyopathy. METHODS AND RESULTS: Pre-treatment with EA was performed 30 min before intraperitoneal injection of LPS. Cardiac function changes in mice of the EA + LPS group were observed using electrocardiography, echocardiography, and enzyme linked immunosorbent assay (ELISA) and compared with the LPS group. The results demonstrated that EA pre-treatment significantly improved the survival rate of septic mice, alleviated the severity of endotoxemia, and exhibited notable cardiac protective effects. These effects were characterized by a reduction in ST-segment elevation on electrocardiography, an increase in ejection fraction (EF) and fraction shortening (FS) on echocardiography and a decrease in the expression of serum cardiac troponin I (cTn-I) levels. Serum exosomes obtained after EA pre-treatment were extracted and administered to septic mice, revealing significant cardiac protective effects of EA-derived exosomes. Furthermore, the antagonism of circulating exosomes in mice markedly suppressed the cardiac protective effects conferred by EA pre-treatment. Analysis of serum exosomes using quantitative reverse transcription-polymerase chain reaction (qRT-PCR) revealed a significant upregulation of miR-381 expression after EA pre-treatment. Inhibition or overexpression of miR-381 through serotype 9 adeno-associated virus (AAV9)-mediated gene delivery demonstrated that overexpression of miR-381 exerted a cardiac protective effect, while inhibition of miR-381 significantly attenuated the cardiac protective effects conferred by EA pre-treatment. CONCLUSIONS: Our research findings have revealed a novel endogenous cardiac protection mechanism, wherein circulating exosomes derived from EA pre-treatment mitigate LPS-induced cardiac dysfunction via miR-381.


Subject(s)
Cardiomyopathies , Electroacupuncture , Exosomes , Lipopolysaccharides , MicroRNAs , Animals , MicroRNAs/genetics , MicroRNAs/metabolism , Exosomes/metabolism , Exosomes/genetics , Electroacupuncture/methods , Mice , Cardiomyopathies/chemically induced , Cardiomyopathies/metabolism , Cardiomyopathies/therapy , Cardiomyopathies/pathology , Cardiomyopathies/genetics , Cardiomyopathies/prevention & control , Lipopolysaccharides/toxicity , Male , Mice, Inbred C57BL , Disease Models, Animal
5.
BMC Cancer ; 24(1): 610, 2024 May 21.
Article in English | MEDLINE | ID: mdl-38773439

ABSTRACT

BACKGROUND: Venous thromboembolism (VTE) is a major complication of breast cancer surgical patients. Assessing VTE awareness enables medical staff to tailor educational programs that improve patient self-management and reduce VTE risk. Therefore, this study aimed to assess VTE awareness among breast cancer surgical patients and identify factors influencing their awareness level. METHODS: A multicenter cross-sectional study was conducted on breast cancer patients scheduled for surgery from May 2023 to November 2023. Data were collected using a general information form and a validated self-assessment questionnaire on VTE awareness for breast cancer surgical patients. Univariate analysis and multiple linear regression analysis were used to analyze the data. RESULTS: Of 1969 patients included, the term awareness rates for deep vein thrombosis and pulmonary embolism were 42.5% and 26.1%, respectively. Information about VTE was primarily obtained from doctors (30.4%), nurses (24.0%), and social media (23.3%). The overall average VTE awareness score was 1.55 ± 0.53, with the dimension of VTE preventive measures scoring highest, and VTE clinical symptoms/signs scoring lowest. Multivariate analysis identified education level, personal VTE history, chemotherapy and surgical history, and the hospital's regional location as significant factors associated with VTE awareness level (p < 0.05). CONCLUSION: This study highlights a critical need for improved VTE awareness among breast cancer surgical patients, particularly regarding clinical symptoms/signs. Health education programs are recommended especially tailored for patients with lower education levels, no history of VTE, or without prior surgery or chemotherapy, to improve their understanding of VTE.


Subject(s)
Breast Neoplasms , Health Knowledge, Attitudes, Practice , Venous Thromboembolism , Humans , Female , Cross-Sectional Studies , Breast Neoplasms/surgery , Breast Neoplasms/complications , Venous Thromboembolism/etiology , Venous Thromboembolism/prevention & control , Venous Thromboembolism/epidemiology , Middle Aged , Adult , Risk Factors , Surveys and Questionnaires , Aged , Postoperative Complications/etiology , Postoperative Complications/epidemiology , Postoperative Complications/prevention & control
7.
Med Image Anal ; 95: 103187, 2024 Jul.
Article in English | MEDLINE | ID: mdl-38705056

ABSTRACT

Domain shift problem is commonplace for ultrasound image analysis due to difference imaging setting and diverse medical centers, which lead to poor generalizability of deep learning-based methods. Multi-Source Domain Transformation (MSDT) provides a promising way to tackle the performance degeneration caused by the domain shift, which is more practical and challenging compared to conventional single-source transformation tasks. An effective unsupervised domain combination strategy is highly required to handle multiple domains without annotations. Fidelity and quality of generated images are also important to ensure the accuracy of computer-aided diagnosis. However, existing MSDT approaches underperform in above two areas. In this paper, an efficient domain transformation model named M2O-DiffGAN is introduced to achieve a unified mapping from multiple unlabeled source domains to the target domain. A cycle-consistent "many-to-one" adversarial learning architecture is introduced to model various unlabeled domains jointly. A condition adversarial diffusion process is employed to generate images with high-fidelity, combining an adversarial projector to capture reverse transition probabilities over large step sizes for accelerating sampling. Considering the limited perceptual information of ultrasound images, an ultrasound-specific content loss helps to capture more perceptual features for synthesizing high-quality ultrasound images. Massive comparisons on six clinical datasets covering thyroid, carotid and breast demonstrate the superiority of the M2O-DiffGAN in the performance of bridging the domain gaps and enlarging the generalization of downstream analysis methods compared to state-of-the-art algorithms. It improves the mean MI, Bhattacharyya Coefficient, dice and IoU assessments by 0.390, 0.120, 0.245 and 0.250, presenting promising clinical applications.


Subject(s)
Ultrasonography , Humans , Ultrasonography/methods , Deep Learning , Algorithms , Image Interpretation, Computer-Assisted/methods
8.
Vet Microbiol ; 293: 110099, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38677125

ABSTRACT

Japanese encephalitis virus (JEV) is a pathogen with a substantial impact on both livestock and human health. However, the critical host factors in the virus life cycle remain poorly understood. Using a library comprising 123411 small guide RNAs (sgRNAs) targeting 19050 human genes, we conducted a genome-wide clustered regularly interspaced short palindromic repeats (CRISPR)/Cas9-based screen to identify essential genes for JEV replication. By employing knockout or knockdown techniques on genes, we identified eleven human genes crucial for JEV replication, such as prolactin releasing hormone receptor (PRLHR), activating signal cointegrator 1 complex subunit 3 (ASCC3), acyl-CoA synthetase long chain family member 3 (ACSL3), and others. Notably, we found that PRLHR knockdown blocked the autophagic flux, thereby inhibiting JEV infection. Taken together, these findings provide effective data for studying important host factors of JEV replication and scientific data for selecting antiviral drug targets.


Subject(s)
CRISPR-Cas Systems , Encephalitis Virus, Japanese , RNA, Guide, CRISPR-Cas Systems , Virus Replication , Virus Replication/genetics , Encephalitis Virus, Japanese/genetics , Encephalitis Virus, Japanese/physiology , Humans , RNA, Guide, CRISPR-Cas Systems/genetics , Gene Library , Animals , Host-Pathogen Interactions/genetics , Encephalitis, Japanese/virology , Cell Line , HEK293 Cells , Clustered Regularly Interspaced Short Palindromic Repeats
9.
Pharm. pract. (Granada, Internet) ; 22(1): 1-10, Ene-Mar, 2024. graf, tab
Article in English | IBECS | ID: ibc-231374

ABSTRACT

Objective: Systemic studies on anti-PD-1 therapy in patients with metastatic colorectal cancer (mCRC) with microsatellite instability or mismatch repair defects are lacking. We aimed to summarize the evidence regarding the efficacy and safety of pembrolizumab, nivolumab, ipilimumab, and tislelizumab in mCRC. Methods: Network meta-analyses (NMAs) can provide comparative efficacy and safety data for clinical decision-making. In this NMA, eligible publications from PubMed, EMBASE, Web of Science, and Cochrane Library from 2016 to April 2023 were identified through a systematic literature review. Literature screening and data extraction were performed according to established criteria. The quality of the literature was evaluated using the Cochrane risk of bias tool, and statistical analysis was performed using Revman5.4 and R language. The main outcome indicators, DCR, ORR, PFS, and OS, were used to evaluate the effectiveness of the drugs, and the main outcome indicators AE and SAE were used to evaluate the safety of each program. Results: Fifteen studies with a sample size of 798 patients were included. In terms of effectiveness, the disease control rate DCR of PD-1 inhibitors was 0.727[95% CI:0.654-0.794]; objective response rate ORR was 0.448[95% CI:0.382-0.514]; and the 1-year progression-free survival rate was 0.551[95% CI:0.458-0.642]. The 1-year overall survival rate was 0.790[95% CI:0.705-0.865]. The adverse events associated with anti-PD-1 were 0.567[95% CI:0.344-0.778] in terms of safety. The total incidence of grade 3 or higher adverse events was 0.241[95% CI:0.174-0.313]. In the subgroup analysis results, the incidence of DCR in the nivolumab + ipilimumab group was 0.826[95% CI:0.780-0.869], the ORR was 0.512[95% CI:0.377-0.647], and the PFS was 0.668[95% CI:0.516-0.804]. The incidence of AE was 0.319 [95% CI:0.039-0.700] and SAE was 0.294 [95% CI:0.171-0.433]... (AU)


Subject(s)
Humans , Colorectal Neoplasms , Neoplasm Metastasis , Nivolumab , Ipilimumab , Pharmaceutical Preparations
10.
ACS Omega ; 9(9): 10160-10168, 2024 Mar 05.
Article in English | MEDLINE | ID: mdl-38463268

ABSTRACT

A simple, feasible, isocratic elution, and stable reversed-phase high performance liquid chromatography method was established and verified. The chromatographic conditions are as follows: EF-C18H, 4.6 × 250 mm, 5 µm column; column temperature 30 °C; for the mobile phase 27.2 g of KH2PO4 and 8.5 g of tetrabutylammonium hydrogen sulfate were taken, 2500 mL of water was added to dissolve, and the pH was adjusted to 6.7 with phosphoric acid:methanol solution with a ratio of 84:16 (V:V). The flow rate was 1.0 mL/min; the injection volume was 10 µL; and the wavelength was 262 nm. According to the current ICH guidelines, the developed method was verified, and the system suitability, specificity, LOD, LOQ, linearity, range, accuracy, repeatability, durability, and solution stability of the proposed method were verified. The validation results demonstrated that the LOQ for the method was 0.05% and the LOD was 0.02%. The content was detected within the concentration range of 300 to 900 µg/mL. The relationship between concentration and measurement was linear, with an r2 of >0.999. The concentration of impurities ranged from 0.3 to 4.5 µg/mL. A good linear correlation was observed within the range of g/mL, with a coefficient of determination r2 greater than 0.999. The accuracy and repeatability met the specified criteria.

11.
Medicine (Baltimore) ; 103(9): e37282, 2024 Mar 01.
Article in English | MEDLINE | ID: mdl-38428903

ABSTRACT

The fear of COVID-19 significantly impacting the health of people globally. This study translated newly developed measurement tool New Fear of the Coronavirus Questionnaire (New_FCQ) into Chinese language and evaluated the psychometric properties of the Chinese version of New_FCQ among Chinese population. A total of 522 participants were included in the study. Internal consistency, construct validity, criterion validity, and concurrent validity of the Chinese version of New_FCQ were assessed in this study. The Chinese version of New_FCQ had excellent internal consistency (α = 0.97) and exploratory factor analysis demonstrated one-dimensional structure of the Chinese version of New_FCQ. The preliminary criterion validity revealed statistically significant differences in the fear of COVID-19 scores based on age and education level (P = .002 and P = .03, respectively). The good concurrent validity also established with the Chinese version Fear of COVID-19 Scale(P < .001). Psychometric proportions of the Chinese version of New_FCQ were established, which exhibited sufficient validity and reliability among Chinese population.


Subject(s)
COVID-19 , Coronavirus , Humans , Psychometrics/methods , Reproducibility of Results , Fear , Surveys and Questionnaires , Language
12.
J Clin Invest ; 134(8)2024 Feb 27.
Article in English | MEDLINE | ID: mdl-38412034

ABSTRACT

Adoptive transfer of T cell receptor-engineered T cells (TCR-T) is a promising strategy for immunotherapy against solid tumors. However, the potential of CD4+ T cells in mediating tumor regression has been neglected. Nasopharyngeal cancer is consistently associated with EBV. Here, to evaluate the therapeutic potential of CD4 TCR-T in nasopharyngeal cancer, we screened for CD4 TCRs recognizing EBV nuclear antigen 1 (EBNA1) presented by HLA-DP5. Using mass spectrometry, we identified EBNA1567-581, a peptide naturally processed and presented by HLA-DP5. We isolated TCR135, a CD4 TCR with high functional avidity, that can function in both CD4+ and CD8+ T cells and recognizes HLA-DP5-restricted EBNA1567-581. TCR135-transduced T cells functioned in two ways: directly killing HLA-DP5+EBNA1+ tumor cells after recognizing EBNA1 presented by tumor cells and indirectly killing HLA-DP5-negative tumor cells after recognizing EBNA1 presented by antigen-presenting cells. TCR135-transduced T cells preferentially infiltrated into the tumor microenvironment and significantly inhibited tumor growth in xenograft nasopharyngeal tumor models. Additionally, we found that 62% of nasopharyngeal cancer patients showed 50%-100% expression of HLA-DP on tumor cells, indicating that nasopharyngeal cancer is well suited for CD4 TCR-T therapy. These findings suggest that TCR135 may provide a new strategy for EBV-related nasopharyngeal cancer immunotherapy in HLA-DP5+ patients.


Subject(s)
Nasopharyngeal Neoplasms , Mice , Animals , Humans , Nasopharyngeal Neoplasms/therapy , Herpesvirus 4, Human , Receptors, Antigen, T-Cell , CD4-Positive T-Lymphocytes , Immunotherapy , Immunotherapy, Adoptive/methods , Tumor Microenvironment
13.
Mol Biol Rep ; 51(1): 351, 2024 Feb 24.
Article in English | MEDLINE | ID: mdl-38400865

ABSTRACT

The nervous system possesses the remarkable ability to undergo changes in order to store information; however, it is also susceptible to damage caused by invading pathogens or neurodegenerative processes. As a member of nucleotide-binding oligomerization domain-like receptor (NLR) family, the NLRP6 inflammasome serves as a cytoplasmic innate immune sensor responsible for detecting microbe-associated molecular patterns. Upon activation, NLRP6 can recruit the adapter protein apoptosis-associated speck-like protein (ASC) and the inflammatory factors caspase-1 or caspase-11. Consequently, inflammasomes are formed, facilitating the maturation and secretion of pro-inflammatory cytokines such as inflammatory factors-18 (IL-18) and inflammatory factors-1ß (IL-1ß). Precise regulation of NLRP6 is crucial for maintaining tissue homeostasis, as dysregulated inflammasome activation can contribute to the development of various diseases. Furthermore, NLRP6 may also play a role in the regulation of extraintestinal diseases. In cells of the brain, such as astrocytes and neurons, NLRP6 inflammasome are also present. Here, the assembly and subsequent activation of caspase-1 mediated by NLRP6 contribute to disease progression. This review aims to discuss the structure and function of NLRP6, explain clearly the mechanisms that induce and activate NLRP6, and explore its role within the central and peripheral nervous system.


Subject(s)
Inflammasomes , Nervous System Diseases , Humans , Inflammasomes/metabolism , Cytokines/metabolism , Caspase 1/metabolism , Apoptosis , Nervous System Diseases/genetics , Caspases , Intracellular Signaling Peptides and Proteins
14.
J Alzheimers Dis ; 97(4): 1661-1672, 2024.
Article in English | MEDLINE | ID: mdl-38306031

ABSTRACT

Background: Rapidly growing healthcare demand associated with global population aging has spurred the development of new digital tools for the assessment of cognitive performance in older adults. Objective: To develop a fully automated Mini-Mental State Examination (MMSE) assessment model and validate the model's rating consistency. Methods: The Automated Assessment Model for MMSE (AAM-MMSE) was an about 10-min computerized cognitive screening tool containing the same questions as the traditional paper-based Chinese MMSE. The validity of the AAM-MMSE was assessed in term of the consistency between the AAM-MMSE rating and physician rating. Results: A total of 427 participants were recruited for this study. The average age of these participants was 60.6 years old (ranging from 19 to 104 years old). According to the intraclass correlation coefficient (ICC), the interrater reliability between physicians and the AAM-MMSE for the full MMSE scale AAM-MMSE was high [ICC (2,1)=0.952; with its 95% CI of (0.883,0.974)]. According to the weighted kappa coefficients results the interrater agreement level for audio-related items showed high, but for items "Reading and obey", "Three-stage command", and "Writing complete sentence" were slight to fair. The AAM-MMSE rating accuracy was 87%. A Bland-Altman plot showed that the bias between the two total scores was 1.48 points with the upper and lower limits of agreement equal to 6.23 points and -3.26 points. Conclusions: Our work offers a promising fully automated MMSE assessment system for cognitive screening with pretty good accuracy.


Subject(s)
Cognitive Dysfunction , Humans , Aged , Aged, 80 and over , Cognitive Dysfunction/diagnosis , Cognitive Dysfunction/psychology , Reproducibility of Results , Neuropsychological Tests , Algorithms , Cognition
15.
Front Microbiol ; 15: 1337994, 2024.
Article in English | MEDLINE | ID: mdl-38298892

ABSTRACT

Sepsis is a condition that greatly impacts the brain, leading to neurological dysfunction and heightened mortality rates, making it one of the primary organs affected. Injury to the central nervous system can be attributed to dysfunction of various organs throughout the entire body and imbalances within the peripheral immune system. Furthermore, central nervous system injury can create a vicious circle with infection-induced peripheral immune disorders. We collate the pathogenesis of septic encephalopathy, which involves microglial activation, programmed cell death, mitochondrial dysfunction, endoplasmic reticulum stress, neurotransmitter imbalance, and blood-brain barrier disruption. We also spotlight the effects of intestinal flora and its metabolites, enterocyte-derived exosomes, cholinergic anti-inflammatory pathway, peripheral T cells and their cytokines on septic encephalopathy.

16.
BMC Biol ; 22(1): 12, 2024 Jan 25.
Article in English | MEDLINE | ID: mdl-38273307

ABSTRACT

BACKGROUND: Many viruses enter host cells by hijacking endosomal trafficking. CapZ, a canonical actin capping protein, participates in endosomal trafficking, yet its precise role in endocytosis and virus infection remains elusive. RESULTS: Here, we showed that CapZ was transiently associated with early endosomes (EEs) and was subsequently released from the matured EEs after the fusion of two EEs, which was facilitated by PI(3)P to PI(3,5)P2 conversion. Vacuolin-1 (a triazine compound) stabilized CapZ at EEs and thus blocked the transition of EEs to late endosomes (LEs). Likewise, artificially tethering CapZ to EEs via a rapamycin-induced protein-protein interaction system blocked the early-to-late endosome transition. Remarkably, CapZ knockout or artificially tethering CapZ to EEs via rapamycin significantly inhibited flaviviruses, e.g., Zika virus (ZIKV) and dengue virus (DENV), or beta-coronavirus, e.g., murine hepatitis virus (MHV), infection by preventing the escape of RNA genome from endocytic vesicles. CONCLUSIONS: These results indicate that the temporal association of CapZ with EEs facilitates early-to-late endosome transition (physiologically) and the release of the viral genome from endocytic vesicles (pathologically).


Subject(s)
Phosphatidylinositol Phosphates , Zika Virus Infection , Zika Virus , Animals , Humans , Mice , Endocytosis/physiology , Endosomes/metabolism , Sirolimus/pharmacology , Sirolimus/metabolism , Transport Vesicles , Virus Internalization , Zika Virus Infection/metabolism
17.
Drug Deliv Transl Res ; 14(7): 2003-2018, 2024 Jul.
Article in English | MEDLINE | ID: mdl-38161194

ABSTRACT

Long noncoding RNAs (lncRNAs) have been demonstrated to participate in neuroblastoma cisplatin resistance and tumorigenesis. LncRNA LINC00460 was previously reported to play a critical regulatory role in many cancer development. Nevertheless, its role in modulating neuroblastoma cisplatin resistance has not been explored till now. Cisplatin-resistant neuroblastoma cell lines were established by exposing neuroblastoma cell lines to progressively increasing concentrations of cisplatin for 6 months. LINC00460, microRNA (miR)-149-5p, and delta-like ligand 1 (DLL1) mRNA expression was measured through RT-qPCR. The protein levels of DLL1, epithelial-to-mesenchymal transition (EMT) markers, and the Notch signaling-related molecules were measured via western blotting. The IC50 value for cisplatin, cell growth, metastasis and apoptosis were analyzed in cisplatin-resistant neuroblastoma cells. The binding between LINC00460 (or DLL1) and miR-149-5p was validated through dual-luciferase reporter assay. The murine xenograft model was established to perform in vivo assays. LINC00460 and DLL1 levels were elevated, while miR-149-5p level was reduced in cisplatin-resistant neuroblastoma cells. LINC00460 depletion attenuated IC50 values for cisplatin, weakened cell growth, metastasis, and EMT, and enhanced apoptosis in cisplatin-resistant neuroblastoma cells. Mechanically, LINC00460 sponged miR-338-3p to increase DLL1 level, thereby activating Notch signaling pathway. DLL1 overexpression antagonized LINC00460 silencing-induced suppression on neuroblastoma cell cisplatin resistance and malignant behaviors, while such effects were further reversed by treatment with DAPT, the inhibitor of Notch pathway. Additionally, LINC00460 knockdown further augmented cisplatin-induced impairment on tumor growth in vivo. LINC00460 contributes to neuroblastoma cisplatin resistance and tumorigenesis through miR-149-5p/DLL1/Notch pathway, providing new directions to improve the therapeutic efficacy of chemotherapy drugs applied in patients with neuroblastoma.


Subject(s)
Calcium-Binding Proteins , Cisplatin , Drug Resistance, Neoplasm , MicroRNAs , Neuroblastoma , RNA, Long Noncoding , Receptors, Notch , Signal Transduction , Cisplatin/pharmacology , MicroRNAs/genetics , Neuroblastoma/genetics , Neuroblastoma/drug therapy , Neuroblastoma/metabolism , Humans , Animals , Drug Resistance, Neoplasm/drug effects , RNA, Long Noncoding/genetics , Cell Line, Tumor , Receptors, Notch/metabolism , Receptors, Notch/genetics , Signal Transduction/drug effects , Calcium-Binding Proteins/genetics , Calcium-Binding Proteins/metabolism , Mice , Mice, Nude , Membrane Proteins/genetics , Membrane Proteins/metabolism , Antineoplastic Agents/pharmacology , Antineoplastic Agents/administration & dosage , Apoptosis/drug effects , Carcinogenesis/drug effects , Carcinogenesis/genetics , Xenograft Model Antitumor Assays , Cell Proliferation/drug effects , Intercellular Signaling Peptides and Proteins/genetics , Intercellular Signaling Peptides and Proteins/metabolism , Mice, Inbred BALB C
18.
Pharm. pract. (Granada, Internet) ; 21(4)oct.- dec. 2023. tab, graf
Article in English | IBECS | ID: ibc-229989

ABSTRACT

Purpose: The aim of this study was to explore the effects of medication therapy management in improving perception, medication adherence, and disease control in UC patients with first-stage of biotherapy. Subjects and Methods: A total of 120 patients with UC who received first-stage biotherapy participated in this study. The patients were divided into MTM group and CFU group. Both groups received three times follow-up, which were carried out at first, third, and sixth discharged month, Group A was followed with the MTM method, and Group B received conventional follow-up. MDRKT was used to assess patient perception, adherence to treatment was assessed by MMSA-8, and we also explored disease control and patient satisfaction. Results: A total of 116 patients completed the survey, the MTM group showed a significant improvement in perception, 84.2% of patients can correctly handle ADEs and 82.5% of patients knew what to do when they leak medication, 87.8% of patients in the MTM group had better adherence than 71.2% in the CPU group (P<0.05). The evaluation of disease control showed that 56.1% of patients in the Group A were in remission which was significantly higher than 32.2% in the Group B (P<0.05). Furthermore, the result of the questionnaire survey showed that perception, ADE, self-management, anxiety, and satisfaction were better in the MTM group than in the CPU group (P<0.05). Conclusion: The MTM group was effective in improving medication adherence, perception, and satisfaction in the patient with ulcerative colitis treated with first-stage biotherapy, and the disease control significantly improved (AU)


Subject(s)
Humans , Male , Female , Adolescent , Young Adult , Adult , Middle Aged , Aged , Aged, 80 and over , Colitis, Ulcerative/drug therapy , Medication Adherence , Biological Therapy , Treatment Outcome
19.
PLoS Pathog ; 19(12): e1011885, 2023 Dec.
Article in English | MEDLINE | ID: mdl-38117848

ABSTRACT

Small RNAs act as fungal pathogen effectors that silence host target genes to promote infection, a virulence mechanism termed cross-kingdom RNA interference (RNAi). The essential pathogen factors of cross-kingdom small RNA production are largely unknown. We here characterized the RNA-dependent RNA polymerase (RDR)1 in the fungal plant pathogen Botrytis cinerea that is required for pathogenicity and cross-kingdom RNAi. B. cinerea bcrdr1 knockout (ko) mutants exhibited reduced pathogenicity and loss of cross-kingdom small RNAs. We developed a "switch-on" GFP reporter to study cross-kingdom RNAi in real-time within the living plant tissue which highlighted that bcrdr1 ko mutants were compromised in cross-kingdom RNAi. Moreover, blocking seven pathogen cross-kingdom small RNAs by expressing a short-tandem target mimic RNA in transgenic Arabidopsis thaliana led to reduced infection levels of the fungal pathogen B. cinerea and the oomycete pathogen Hyaloperonospora arabidopsidis. These results demonstrate that cross-kingdom RNAi is significant to promote host infection and making pathogen small RNAs an effective target for crop protection.


Subject(s)
Arabidopsis , RNA-Dependent RNA Polymerase , RNA Interference , RNA, Small Interfering/genetics , RNA-Dependent RNA Polymerase/genetics , Arabidopsis/genetics , Arabidopsis/microbiology , Virulence/genetics , Plants/genetics , Botrytis/genetics , Plant Diseases/genetics , Plant Diseases/microbiology , RNA, Fungal/genetics , RNA, Plant
20.
BMC Public Health ; 23(1): 2257, 2023 11 16.
Article in English | MEDLINE | ID: mdl-37974168

ABSTRACT

BACKGROUND: The growing prevalence of smartphone use among college students in China has led to health concerns, including De Quervain's Tenosynovitis (DQT). However, the specific smartphone usage behaviors contributing to DQT remain poorly understood. This study aimed to explore the relationship between smartphone usage behaviors and DQT in college students. METHODS: A cross-sectional study was conducted with 937 students from various majors in Guangxi between September 2021 and April 2022. Participants completed an online questionnaire assessing smartphone usage behaviors and their association with DQT. The Finkelstein test was employed to diagnose DQT. RESULTS: Over half of the college students (52%) tested positive for DQT via Finkelstein's test. Higher levels of smartphone usage time (6-8 h/day: OR = 4.454, 95%CI:1.662-12.229; ≥8 h/day: OR = 4.521, 95%CI:1.596-12.811), phone games (OR = 1.997, 95%CI:1.312-3.040), social media (OR = 2.263, 95%CI:1.795-3.833), and leisure activities (OR = 1.679, 95%CI:1.140-2.475) were significantly associated with an increased risk of DQT. Two specific gestures (Bilateral thumbs, BT: OR = 1.900, 95%CI:1.281-2.817; Bilateral thumbs-horizontal screen, BT-HS: OR = 1.872, 95%CI:1.244-2.818) and two screen sizes (5.0-5.5inch: OR = 2.064, 95%CI:1.108-3.846; 6.0-6.5inch: OR = 2.413, 95%CI:1.125-4.083) also exhibited a higher risk of DQT. Bilateral DQT was observed, with Gesture-BT identified as the primary risk factor. CONCLUSION: Our findings suggest that increased smartphone usage time, phone games, social media, and leisure activities elevate the risk of DQT among college students. Furthermore, two specific gestures and two screen sizes were also linked to a heightened DQT risk. To mitigate DQT development, college students should reduce smartphone usage time and adopt appropriate gestures.


Subject(s)
De Quervain Disease , Tenosynovitis , Humans , Tenosynovitis/complications , De Quervain Disease/complications , De Quervain Disease/diagnosis , De Quervain Disease/epidemiology , Smartphone , Cross-Sectional Studies , China/epidemiology , Students
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