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In the past decade, chimeric antigen receptor (CAR)-T cell therapy has emerged as a promising immunotherapeutic approach for combating cancers, demonstrating remarkable efficacy in relapsed/refractory hematological malignancies in both pediatric and adult patients. CAR-natural killer (CAR-NK) cell complements CAR-T cell therapy by offering several distinct advantages. CAR-NK cells do not require HLA compatibility and exhibit low safety concerns. Moreover, CAR-NK cells are conducive to "off-the-shelf" therapeutics, providing significant logistic advantages over CAR-T cells. Both CAR-T and CAR-NK cells have shown consistent and promising results in hematological malignancies. However, their efficacy against solid tumors remains limited due to various obstacles including limited tumor trafficking and infiltration, as well as an immuno-suppressive tumor microenvironment. In this review, we discuss the recent advances and current challenges of CAR-T and CAR-NK cell immunotherapies, with a specific focus on the obstacles to their application in solid tumors. We also analyze in depth the advantages and drawbacks of CAR-NK cells compared to CAR-T cells and highlight CAR-NK CAR optimization. Finally, we explore future perspectives of these adoptive immunotherapies, highlighting the increasing contribution of cutting-edge biotechnological tools in shaping the next generation of cellular immunotherapy.
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ARHGAP25, a member of the ARHGAP family, encodes a negative regulator of Rho-GTPase that is important for actin remodeling, cell polarity, and cell migration. ARHGAP25 is down-regulated in a variety of solid tumors and promotes cancer cell growth, migration, and invasion. However, nothing is understood about ARHGAP25's biological function in osteosarcoma. This work used qPCR and WB to confirm the expression of ARHGAP25 in osteosarcoma following the initial analysis of its expression in pan-cancer. For GO and KEGG analysis, we have chosen 300 genes from the TARGET osteosarcoma data that had the strongest positive correlation with ARHGAP25, and we created nomogram and calibration charts. We simultaneously overexpressed ARHGAP25 in osteosarcoma cells to examine its impact on apoptosis and proliferation. By using MSP, we determined their methylation status in osteosarcoma cells and normal bone cells. We observed that ARHGAP25 was significantly downregulated in a range of malignancies, including osteosarcoma, and was associated with poor patient outcomes. The decrease of ARHGAP25 expression in osteosarcoma is related to DNA methylation. Overexpression of ARHGAP25 induced apoptosis and inhibited the proliferation of osteosarcoma cells in vitro. In addition, ARHGAP25 is also associated with immune-related pathways in osteosarcoma. These findings suggest that ARHGAP25 is a valuable prognostic biomarker in osteosarcoma patients.
Subject(s)
Apoptosis , Bone Neoplasms , Cell Proliferation , Computational Biology , DNA Methylation , GTPase-Activating Proteins , Gene Expression Regulation, Neoplastic , Osteosarcoma , Osteosarcoma/genetics , Osteosarcoma/pathology , Osteosarcoma/metabolism , Humans , GTPase-Activating Proteins/genetics , GTPase-Activating Proteins/metabolism , Computational Biology/methods , Bone Neoplasms/genetics , Bone Neoplasms/pathology , Bone Neoplasms/metabolism , Bone Neoplasms/mortality , Apoptosis/genetics , Cell Line, Tumor , Cell Proliferation/genetics , Prognosis , Male , Female , Biomarkers, Tumor/genetics , Biomarkers, Tumor/metabolism , Clinical RelevanceABSTRACT
This study aims at extensively investigating the explosion characteristics of a hybrid mixture of gas and coal dust. Accordingly, the standard 20 L spherical explosion system was applied to measure parameters such as the lower explosion limit, maximum explosion pressure, and index of the hybrid mixture of different concentrations of gas and coal dust. Moreover, different coal dust particle sizes and components were measured. With regard to coal dust with different particle sizes and components, the obtained results revealed that, while the addition of gas significantly reduced the lower explosion limit, the maximum explosion pressure and index were increased; that is to say, the presence of gas will increase the explosion risk of coal dust. However, under conditions in which the particle size of the coal dust was large or the volatile content was low, the addition of gas was found to lead to a higher decrease of the lower explosion limit; this is, while the maximum explosion pressure and explosion index were increased. Consequently, gas can be argued to have a greater influence on the explosion risk of coal dust with a large particle size or low volatile content. Furthermore, regardless of the particle size or the volatile content of coal dust, the maximum explosion pressure and explosion index of the hybrid mixture were observed to be higher than that of the pure coal dust but lower than that of the pure gas. That is to say, the explosion intensity of the gas/coal dust composite system is higher than that of pure coal dust but less than that of pure gas. The research results can provide theoretical basis for coal mine explosion disaster prevention and control and have important significance.
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Lung cancer is a malignant tumor with highly heterogeneous characteristics. A classic Chinese medicine, Pinellia ternata (PT), was shown to exert therapeutic effects on lung cancer cells. However, its chemical and pharmacological profiles are not yet understood. In the present study, we aimed to reveal the mechanism of PT in treating lung cancer cells through metabolomics and network pharmacology. Metabolomic analysis of two strains of lung cancer cells treated with Pinellia ternata extracts (PTE) was used to identify differentially abundant metabolites, and the metabolic pathways associated with the DEGs were identified by MetaboAnalyst. Then, network pharmacology was applied to identify potential targets against PTE-induced lung cancer cells. The integrated network of metabolomics and network pharmacology was constructed based on Cytoscape. PTE obviously inhibited the proliferation, migration and invasion of A549 and NCI-H460 cells. The results of the cellular metabolomics analysis showed that 30 metabolites were differentially expressed in the lung cancer cells of the experimental and control groups. Through pathway enrichment analysis, 5 metabolites were found to be involved in purine metabolism, riboflavin metabolism and the pentose phosphate pathway, including D-ribose 5-phosphate, xanthosine, 5-amino-4-imidazolecarboxyamide, flavin mononucleotide (FMN) and flavin adenine dinucleotide (FAD). Combined with network pharmacology, 11 bioactive compounds were found in PT, and networks of bioactive compound-target gene-metabolic enzyme-metabolite interactions were constructed. In conclusion, this study revealed the complicated mechanisms of PT against lung cancer. Our work provides a novel paradigm for identifying the potential mechanisms underlying the pharmacological effects of natural compounds.
Subject(s)
Carcinoma, Non-Small-Cell Lung , Lung Neoplasms , Metabolomics , Network Pharmacology , Pinellia , Humans , Carcinoma, Non-Small-Cell Lung/drug therapy , Carcinoma, Non-Small-Cell Lung/metabolism , Lung Neoplasms/drug therapy , Lung Neoplasms/metabolism , Cell Line, Tumor , Plant Extracts/pharmacology , A549 Cells , Drugs, Chinese Herbal/pharmacology , Cell Proliferation/drug effectsABSTRACT
BACKGROUND: Artificial intelligence (AI) technologies, particularly large language models (LLMs), have been widely employed by the medical community. In addressing the intricacies of urology, ChatGPT offers a novel possibility to aid in clinical decision-making. This study aimed to investigate the decision-making ability of LLMs in solving complex urology-related problems and assess its effectiveness in providing psychological support to patients with urological disorders. MATERIALS AND METHODS: This study evaluated the clinical and psychological support capabilities of ChatGPT 3.5 and 4.0 in the field of urology. A total of 69 clinical and 30 psychological questions were posed to the AI models, and their responses were evaluated by both urologists and psychologists. As a control, clinicians from Chinese medical institutions provided responses under closed-book conditions. Statistical analyses were conducted separately for each subgroup. RESULTS: In multiple-choice tests covering diverse urological topics, ChatGPT 4.0, performed comparably to the physician group, with no significant overall score difference. Subgroup analyses revealed variable performance, based on disease type and physician experience, with ChatGPT 4.0 generally outperforming ChatGPT 3.5 and exhibiting competitive results against physicians. When assessing the psychological support capabilities of AI, it is evident that ChatGPT4.0 outperforms ChatGPT3.5 across all urology-related psychological problems. CONCLUSIONS: The performance of LLMs in dealing with standardized clinical problems and providing psychological support has certain advantages over clinicians. AI stands out as a promising tool for potential clinical aid.
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The organic-inorganic lead halide per materials have emerged as highly promising contenders in the field of photovoltaic technology, offering exceptional efficiency and cost-effectiveness. The commercialization of perovskite photovoltaics hinges on successfully transitioning from lab-scale perovskite solar cells to large-scale perovskite solar modules (PSMs). However, the efficiency of PSMs significantly diminishes with increasing device area, impeding commercial viability. Central to achieving high-efficiency PSMs is fabricating uniform functional films and optimizing interfaces to minimize energy loss. This review sheds light on the path toward large-scale PSMs, emphasizing the pivotal role of integrating cutting-edge scientific research with industrial technology. By exploring scalable deposition techniques and optimization strategies, the advancements and challenges in fabricating large-area perovskite films are revealed. Subsequently, the architecture and contact materials of PSMs are delved while addressing pertinent interface issues. Crucially, efficiency loss during scale-up and stability risks encountered by PSMs is analyzed. Furthermore, the advancements in industrial efforts toward perovskite commercialization are highlighted, emphasizing the perspective of PSMs in revolutionizing renewable energy. By highlighting the scientific and technical challenges in developing PSMs, the importance of combining science and industry to drive their industrialization and pave the way for future advancements is stressed.
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BACKGROUND: The accurate diagnosis and effective management of arrhythmias are crucial, with nurses playing a key role in the early detection and treatment, significantly impacting patient outcomes. Improving education on arrhythmias among nurses, especially in critical care and perioperative settings, can enhance patient safety and the quality of care. METHODS: A total of 116 trainee nurses were randomly divided into two groups: one utilizing the conceive-design-implement-operate (CDIO) model and the other employing a traditional lecture-based learning (LBL) method, to undergo arrhythmia training. The studyassessed the effects of the two teaching methods and investigated the students' attitudes toward these educational practices, with all participants completing pre- and post-course tests. RESULTS: The CDIO model significantly enhances nursing students' arrhythmia proficiency, yielding higher test scores and sustained improvement after 24-week compared to the traditional LBL method, alongside markedly better self-learning enthusiasm, understanding, satisfaction with the teaching approach and effectiveness, and interest in learning arrhythmia. The CDIO model in nursing arrhythmia courses boosts theoretical knowledge and application, showing potential in clinical skill enhancement. CONCLUSIONS: Our study introduces the CDIO model in nursing arrhythmia courses, with improvement in knowledge and skills, and promise for broader application.
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BACKGROUND: Antioxidant and pro-oxidant dietary patterns and lifestyle changes have been considered to play a crucial role in Helicobacter pylori (H. pylori) infection. We conducted this study to investigate the underlying association between oxidative balance score (OBS) and H. pylori infection in the US population. METHODS: This was a cross-sectional study according to data from the National Health and Nutrition Examination Survey (1999-2000), and included individuals with complete information about dietary intake and H. pylori serologic testing results. In the present study, we used multivariate logistic regression analysis, smoothed curve fitting, subgroup analyses, and Cox proportional hazards modeling based on demographic and clinical variables to examine the relationship between OBS and H. pylori infection. RESULTS: A total of 3413 individuals participated in our analysis with an average age of 32.31 years. The prevalence of H. pylori infection in the study population was 29.77%. By performing smooth curve fitting analysis, we observed an approximately linear relationship between OBS and H. pylori infection, indicating that lower OBS was associated with higher risk of H. pylori infection, especially in over 60 years of age and non-Hispanic white populations. All-cause mortality was also found lower in individuals with higher OBS levels. CONCLUSION: In the US population, increased levels of OBS were associated with a reduced risk of H. pylori infection and decreased all-cause mortality. More and further work is still needed to elucidate the precise mechanism of the association between OBS and H. pylori infection.
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Background: While nanoplatform-based cancer theranostics have been researched and investigated for many years, enhancing antitumor efficacy and reducing toxic side effects is still an essential problem. Methods: We exploited nanoparticle coordination between ferric (Fe2+) ions and telomerase-targeting hairpin DNA structures to encapsulate doxorubicin (DOX) and fabricated Fe2+-DNA@DOX nanoparticles (BDDF NPs). This work studied the NIR fluorescence imaging and pharmacokinetic studies targeting the ability and biodistribution of BDDF NPs. In vitro and vivo studies investigated the nano formula's toxicity, imaging, and synergistic therapeutic effects. Results: The enhanced permeability and retention (EPR) effect and tumor targeting resulted in prolonged blood circulation times and high tumor accumulation. Significantly, BDDF NPs could reduce DOX-mediated cardiac toxicity by improving the antioxidation ability of cardiomyocytes based on the different telomerase activities and iron dependency in normal and tumor cells. The synergistic treatment efficacy is enhanced through Fe2+-mediated ferroptosis and the ß-catenin/p53 pathway and improved the tumor inhibition rate. Conclusion: Harpin DNA-based nanoplatforms demonstrated prolonged blood circulation, tumor drug accumulation via telomerase-targeting, and synergistic therapy to improve antitumor drug efficacy. Our work sheds new light on nanomaterials for future synergistic chemotherapy.
Subject(s)
Doxorubicin , Telomerase , Doxorubicin/chemistry , Doxorubicin/pharmacokinetics , Doxorubicin/pharmacology , Doxorubicin/administration & dosage , Animals , Humans , Telomerase/metabolism , Cell Line, Tumor , Mice , DNA/chemistry , DNA/pharmacokinetics , DNA/administration & dosage , Tissue Distribution , Nanoparticles/chemistry , Neoplasms/drug therapy , Ferroptosis/drug effects , Antibiotics, Antineoplastic/pharmacology , Antibiotics, Antineoplastic/pharmacokinetics , Antibiotics, Antineoplastic/chemistry , Antibiotics, Antineoplastic/administration & dosage , Mice, Inbred BALB C , Drug Carriers/chemistry , Drug Carriers/pharmacokineticsABSTRACT
This work reports the nonlinear dynamics of a mid-infrared interband cascade laser (ICL) subject to optical injection. It is shown that the stable locking regime is asymmetric and broadens with increasing injection strength. Outside the locking regime, the ICL mostly produces period-one oscillations. However, three categories of periodic pulse oscillations are observed in the vicinity of the Hopf bifurcation and the saddle-node bifurcation. In particular, it is found that the ICL generates broadband chaos at a near-threshold pump current, and the chaos bandwidth is over 300 MHz.
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Podocytopathies, such as focal segmental glomerulosclerosis (FSGS), are characterized by podocyte injury and can easily progress to end-stage kidney disease. However, the mechanisms underlying podocyte injury remain unclear. We observed podocyte injury along with pyroptosis in patients with FSGS. Bioinformatic analysis of public datasets revealed that transmembrane protein 30a (Tmem30a) might be associated with FSGS. The expression of Temem30a and the podocyte-related protein, nephrin, were significantly downregulated in patients with FSGS, adriamycin (ADR)-induced mice, and podocyte-specific Tmem30a lox P /loxP ; NPHS2-Cre mice, whereas the expression of NLR family pyrin domain containing 3 (NLRP3) and ASC, two pyroptosis-related proteins, were significantly upregulated. Meanwhile, the pyroptosis inhibitor MCC950 and disulfiram (DSF) increased Tmem30a and podocyte-related proteins expression, and inhibited pyroptosis-related proteins expression in ADR-induced mouse podocytes and Tmem30a knockdown (KD) mouse podocytes. Therefore, Tmem30a might protect against podocyte injury by inhibiting pyroptosis, suggesting a potential therapeutic target for podocytopathies.
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Temperature's influence on the physical and mechanical properties of rocks is a crucial concern for the rational design of deep rock engineering structures and the assurance of their long-term stability. To systematically comprehend the impact of the evolution of mineral composition and micro characteristics on the physical and mechanical behavior of thermally damaged granite, we observed the microscopic structural defects inside the rocks with a polarizing microscope and revealed the thermal damage mechanism of granite from a microscopic perspective by combining ultrasound detection and XRD phase characteristic analysis. The results show that the physical properties of the specimens changed significantly at three characteristic temperature points: 400 °C, 800 °C, and 1000 °C. Under high temperature conditions, the diffraction intensity of all minerals in granite, except for quartz, generally decreased, and stable minerals decomposed. Albite and potash feldspar decomposed to form anorthoclase, thereby reducing the structural stability of the rock material. In addition, the peak width of various minerals decreased to varying degrees with increasing temperature. The increase in mineral volume further damaged the internal structure of the rock material while promoting the transformation from grain boundary to intergranular cracks and from intragranular cracks to transgranular cracks, ultimately forming a interconnected crack network. Thermal damage significantly reduced the longitudinal wave velocity, uniaxial compressive strength, and elastic modulus of the specimens, while the stress-strain curve relationship indicated that the specimens underwent two opposite processes of transformation from brittleness to ductility and then from ductility to brittleness. The thermal damage threshold of granite in this study was 600 °C.
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Natural killer (NK) cells have clinical potential against cancer; however, multiple limitations hinder the success of NK cell therapy. Here, we performed unbiased functional mapping of tumor-infiltrating NK (TINK) cells using in vivo adeno-associated virus (AAV)-SB (Sleeping Beauty)-CRISPR (clustered regularly interspaced short palindromic repeats) screens in four solid tumor mouse models. In parallel, we characterized single-cell transcriptomic landscapes of TINK cells, which identified previously unexplored subpopulations of NK cells and differentially expressed TINK genes. As a convergent hit, CALHM2-knockout (KO) NK cells showed enhanced cytotoxicity and tumor infiltration in mouse primary NK cells and human chimeric antigen receptor (CAR)-NK cells. CALHM2 mRNA reversed the CALHM2-KO phenotype. CALHM2 KO in human primary NK cells enhanced their cytotoxicity, degranulation and cytokine production. Transcriptomics profiling revealed CALHM2-KO-altered genes and pathways in both baseline and stimulated conditions. In a solid tumor model resistant to unmodified CAR-NK cells, CALHM2-KO CAR-NK cells showed potent in vivo antitumor efficacy. These data identify endogenous genetic checkpoints that naturally limit NK cell function and demonstrate the use of CALHM2 KO for engineering enhanced NK cell-based immunotherapies.
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Near-infrared semiconductor lasers subject to optical feedback usually produce chaos with a broad bandwidth of a few GHz. However, the reported mid-infrared interband cascade lasers (ICLs) only show chaos with a limited bandwidth below 1â GHz. Here we show that an ICL with optical feedback is able to generate broadband chaos as well. The mid-infrared chaos exhibits a remarkable bandwidth of about 6â GHz, which is comparable to that of the near-infrared counterpart. In addition, the spectral coverage in the electrical domain reaches as high as 17.7â GHz. It is found that the chaos bandwidth generally broadens with increasing feedback ratio and/or increasing pump current of the laser, while it is insensitive to the feedback length.
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Introduction: Cervical cancer (CC) ranks as the fourth most prevalent malignant tumor among women worldwide, and is the fourth leading cause of cancer-related mortality. GuiErBai (GEB), a compound preparation developed by our research team, is derived from the ancient Chinese medicine of the Miao nationality and is comprised of podophyllotoxin (PTOX), imperatorin, isoimperatorin, and A. dahurica alkaloids. These individual components have demonstrated notable efficacy in tumor treatment. However, the specific anti-tumor effect of the compound Chinese medicine GEB in the context of CC has yet to be validated. Methods: HeLa and SiHa cell lines were utilized for in vitro experiments and treated with 5 mg/mL and 10 mg/mL GEB concentrations, respectively. The cell cycle changes after GEB treatment were assessed using flow cytometry. Transmission electron microscopy was employed to observe autophagic bodies and apoptotic bodies, while MDC staining evaluated the occurrence of autophagy. CCK-8 was used to observe the effect of GEB on cell proliferation, and Transwell assays assessed cell migration and invasion. Western blotting detected cell cycle and apoptosis-related protein expression, along with the expression level of autophagy-related protein LC3I/II. Changes in ROS and mitochondrial membrane potential in cervical cancer cells following GEB treatment were determined using ROS detection and mitochondrial membrane potential detection kits. For the in vivo experiment, a nude mouse model of cervical cancer transplantation based on HeLa cells was established. Experimental animals were divided into negative control, positive control, high-dose GEB (10 mg/mL), and low-dose GEB (5 mg/mL) groups. Results: In HeLa and SiHa cell lines, the G0/G1 phase of tumor cells significantly decreased (p < 0.001), while the G2/M phase increased notably (p < 0.001) following various GEB treatments. Electron microscopy showed GEB promoted apoptotic body and autophagosome formation in both cell lines. Compared to untreated HeLa and SiHa cells, GEB-treated cells exhibited significantly reduced caspase3 protein expression, and substantially increased autophagy-related protein LC3I/II expression. GEB treatment significantly reduced migration and invasion capabilities in both cell lines (p < 0.001), while ROS content and mitochondrial membrane potential were significantly elevated (p < 0.001). GEB effectively inhibited cervical cancer cell proliferation, with the optimal concentration being 10 mg/mL. A successful nude mouse model of cervical cancer transplantation was established using HeLa cells. Post-GEB treatment, the tumor volume and weight in nude mice significantly decreased (p < 0.001), with diminished expression of CD34, VEGF, and caspase3 proteins in tumor tissues. Discussion: GEB exhibits a robust antitumor effect against cervical cancer, both in vitro and in vivo, in a concentration-dependent manner, by regulating autophagy and apoptosis of tumor cells.
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Nauclea officinalis is a Chinese medicinal material with a high medicinal value, which contains various chemical constituents such as alkaloids, pentacyclic triterpenoids and their saponins, organic phenolic acids and their glycosides, iridoids, and flavonoids. It has antiviral, antibacterial, antipyretic, analgesic, anti-inflammatory, and immunoregulatory functions. This article systematically reviewed the reported chemical constituents and pharmacological effects of N. officinalis. According to the concept of quality markers, the quality markers of N. officinalis were predicted and analyzed from the aspects of plant kinship, specificity of chemical constituents, traditional drug efficacy, measurability of chemical constituents, plasma components, and different producing areas and harvest times, in order to provide a basis for the quality evaluation of N. officinalis.
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Drugs, Chinese Herbal , Drugs, Chinese Herbal/chemistry , Drugs, Chinese Herbal/pharmacology , Humans , Animals , Rubiaceae/chemistry , Quality ControlABSTRACT
The involvement of Interferon-stimulated exonuclease gene 20 (ISG20) has been reported in renal clear cell carcinoma, hepatocellular carcinoma, and cervical cancer. However, its role in ovarian cancer chemotherapy remains unclear. In this study, we conducted a comparative analysis of TGF-ß1 and ISG20 in cisplatin-sensitive and cisplatin-resistant ovarian cancer cells and tissues using qRT-PCR and a tissue immunofluorescence analysis. We also investigated the impact of ISG20-targeted drugs (IFN-γ) and TGF-ß1 inhibitors on cisplatin response both in vivo and in vitro. Additionally, we assessed the effects of TGF-ß1 or ISG20 on the polarization of tumor-associated macrophages through flow cytometry and ELISA analysis. Our findings revealed that ISG20 expression was lower in cisplatin-resistant tissues compared to cisplatin-sensitive tissues; however, overexpression of ISG20 sensitized ovarian cancer to cisplatin treatment. Furthermore, activation of ISG20 expression with IFN-γ or TGF-ß1 inhibitors enhanced the sensitivity of ovarian cancer cells to cisplatin therapy. Notably, our results demonstrated that TGF-ß1 promoted M2-type macrophage polarization as well as PI3K/mTOR pathway activation by suppressing ISG20 expression both in vivo and in vitro. In conclusion, our study highlights the critical role played by ISG20 within the network underlying cisplatin resistance in ovarian cancer. Targeting ISG20 using IFN-γ or TGF-ß1 inhibitors may represent a promising therapeutic strategy for treating ovarian cancer.
Subject(s)
Antineoplastic Agents , Cisplatin , Drug Resistance, Neoplasm , Ovarian Neoplasms , Phosphatidylinositol 3-Kinases , Signal Transduction , TOR Serine-Threonine Kinases , Transforming Growth Factor beta1 , Cisplatin/pharmacology , Cisplatin/therapeutic use , Female , Humans , TOR Serine-Threonine Kinases/metabolism , Transforming Growth Factor beta1/metabolism , Ovarian Neoplasms/drug therapy , Ovarian Neoplasms/metabolism , Ovarian Neoplasms/immunology , Signal Transduction/drug effects , Animals , Phosphatidylinositol 3-Kinases/metabolism , Antineoplastic Agents/pharmacology , Antineoplastic Agents/therapeutic use , Cell Line, Tumor , Drug Resistance, Neoplasm/drug effects , Mice , Macrophages/immunology , Macrophages/drug effects , Macrophages/metabolism , Interferon-gamma/metabolism , Mice, Nude , Mice, Inbred BALB C , Intracellular Signaling Peptides and ProteinsABSTRACT
Background: Observational studies have indicated a possible connection between Helicobacter pylori (H. pylori) infection and eosinophilic esophagitis (EoE), but their causal relationship has yet to be established. To investigate the causal associations between H. pylori infection and EoE, we performed a Mendelian randomization (MR) analysis. Methods: Firstly, we conducted both univariable and multivariable Mendelian randomization (MR) analyses. Furthermore, a two-step MR was carried out to ascertain the potential underlying pathways of these associations, particularly the involvement of inflammatory cytokines. We employed the inverse-variance weighted (IVW) method as the main analysis in our MR study. To enhance the credibility of the results, we also conducted several sensitivity analyses. Results: Our study demonstrated a noteworthy correlation between genetically predicted anti-H. pylori IgG antibody levels and a reduced risk of EoE (OR=0.325, 95% CI=0.165-0.643, P value=0.004, adj p value=0.009). No significant causal associations were detected between other H. pylori antibodies and EoE in our study. When it comes to multivariable MR analysis controlling for education attainment, household income, and deprivation individually, the independent causal impact of anti-H. pylori IgG on EoE persisted. Surprisingly, the two-step MR analysis indicated that inflammatory factors (IL-4, IL-5, IL-13, IL-17, and IFN-γ) did not appear to mediate the protective effect of H. pylori infection against EoE. Conclusion: Findings suggested that among the range of H. pylori-related antibodies, anti-H. pylori IgG antibody is the sole causal factor associated with protection against EoE. Certain inflammatory factors may not be involved in mediating this association. These findings make a significant contribution to advancing our understanding of the pathogenesis of EoE and its evolving etiology.
Subject(s)
Antibodies, Bacterial , Eosinophilic Esophagitis , Helicobacter Infections , Helicobacter pylori , Mendelian Randomization Analysis , Humans , Helicobacter Infections/immunology , Helicobacter Infections/complications , Eosinophilic Esophagitis/immunology , Eosinophilic Esophagitis/genetics , Eosinophilic Esophagitis/epidemiology , Eosinophilic Esophagitis/etiology , Eosinophilic Esophagitis/microbiology , Helicobacter pylori/immunology , Antibodies, Bacterial/blood , Antibodies, Bacterial/immunology , Immunoglobulin G/blood , Immunoglobulin G/immunology , Polymorphism, Single Nucleotide , Cytokines , Genetic Predisposition to DiseaseABSTRACT
Background: During the use of electronic cigarettes (e-cigarettes), users are still exposed to carcinogens similar to those found in tobacco products. Since these carcinogens are metabolized and excreted in urine, they may have carcinogenic effects on the bladder urinary tract epithelium. This meta-analysis aimed to compare bladder cancer carcinogens in the urine of tobacco users and e-cigarette users using a large number of samples. Methods: A systematic meta-analysis was performed using data obtained from several scientific databases (up to November 2023). This cumulative analysis was performed following the Preferred Reporting Items for Systematic Evaluation and Meta-Analysis (PRISMA) and Assessing the Methodological Quality of Systematic Evaluations (AMSTAR) guidelines, according to a protocol registered with PROSPERO. This study was registered on PROSPERO and obtained the unique number: CRD42023455600. Results: The analysis included 10 high-quality studies that considered polycyclic aromatic hydrocarbons (PAHs), volatile organic compounds (VOCs) and tobacco-specific nitrosamines (TSNAs). Statistical indicators show that there is a difference between the tobacco user group and the e-cigarette user group in terms of 1-Hydroxynaphthalene (1-NAP) [weighted mean difference (WMD)10.14, 95% confidence interval (CI) (8.41 to 11.88), p < 0.05], 1-Hydroxyphenanthrene (1-PHE) [WMD 0.08, 95% CI (-0.14 to 0.31), p > 0.05], 1-Hydroxypyrene (1-PYR) [WMD 0.16, 95% CI (0.12 to 0.20), p < 0.05], 2-Hydroxyfluorene (2-FLU) [WMD 0.69, 95% CI (0.58 to 0.80), p < 0.05], 2-Hydroxynaphthalene (2-NAP) [WMD 7.48, 95% CI (4.15 to 10.80), p < 0.05], 3-Hydroxyfluorene (3-FLU) [WMD 0.57, 95% CI (0.48 to 0.66), p < 0.05], 2-Carbamoylethylmercapturic acid (AAMA) [WMD 66.47, 95% CI (27.49 to 105.46), p < 0.05], 4-Hydroxy-2-buten-1-yl-mercapturic acid (MHBMA) [WMD 287.79, 95% CI (-54.47 to 630.04), p > 0.05], 4-(Methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNAL) [WMD 189.37, 95% CI (78.45 to 300.29), p < 0.05], or N0-nitrosonornicotine (NNN) [WMD 11.66, 95% CI (7.32 to 16.00), p < 0.05]. Conclusion: Urinary bladder cancer markers were significantly higher in traditional tobacco users than in e-cigarette users.Systematic review registration: PROSPERO (CRD42023455600: https://www.crd.york.ac.uk/PROSPERO/).