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1.
Int J Chron Obstruct Pulmon Dis ; 19: 1491-1513, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38957709

RESUMO

Background: Chronic obstructive pulmonary disease (COPD) stands as a predominant cause of global morbidity and mortality. This study aims to elucidate the relationship between pyroptosis-related genes (PRGs) and COPD diagnosis in the context of immune infiltration, ultimately proposing a PRG-based diagnostic model for predicting COPD outcomes. Methods: Clinical data and PRGs of COPD patients were sourced from the GEO database. The "ConsensusClusterPlus" package was employed to generate molecular subtypes derived from PRGs that were identified through differential expression analysis and LASSO Cox analysis. A diagnostic signature including eight genes (CASP4, CASP5, ELANE, GPX4, NLRP1, GSDME, NOD1and IL18) was also constructed. Immune cell infiltration calculated by the ESTIMATE score, Stroma scores and Immune scores were also compared on the basis of pyroptosis-related molecular subtypes and the risk signature. We finally used qRT - PCR to detect the expression levels of eight genes in COPD patient and normal. Results: The diagnostic model, anchored on eight PRGs, underwent validation with an independent experimental cohort. The area under the receiver operating characteristic (ROC) curves (AUC) for the diagnostic model showcased values of 0.809, 0.765, and 0.956 for the GSE76925, GSE8545, and GSE5058 datasets, respectively. Distinct expression patterns and clinical attributes of PRGs were observed between the comparative groups, with functional analysis underscoring a disparity in immune-related functions between them. Conclusion: In this study, we developed a potential as diagnostic biomarkers for COPD and have a significant role in modulating the immune response. Such insights pave the way for novel diagnostic and therapeutic strategies for COPD.


Assuntos
Bases de Dados Genéticas , Valor Preditivo dos Testes , Doença Pulmonar Obstrutiva Crônica , Piroptose , Humanos , Doença Pulmonar Obstrutiva Crônica/genética , Doença Pulmonar Obstrutiva Crônica/diagnóstico , Doença Pulmonar Obstrutiva Crônica/imunologia , Piroptose/genética , Perfilação da Expressão Gênica , Pulmão/imunologia , Masculino , Feminino , Pessoa de Meia-Idade , Marcadores Genéticos , Estudos de Casos e Controles , Transcriptoma , Idoso , Reprodutibilidade dos Testes , Predisposição Genética para Doença , Prognóstico
2.
BMC Infect Dis ; 24(1): 656, 2024 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-38956526

RESUMO

OBJECTIVE: To investigate risk factors associated with long-term mortality in patients with stage II and III tuberculous meningitis (TBM). METHODS: This retrospective analysis examined patients who were first diagnosed with stage II and III TBM at West China Hospital of Sichuan University between January 1, 2018 and October 1, 2019. Patients were followed via telephone and categorized into survival and mortality groups based on 4-year outcomes. Multivariate logistic regression identified independent risk factors for long-term mortality in stage II and III TBM. RESULTS: In total, 178 patients were included, comprising 108 (60.7%) males and 36 (20.2%) non-survivors. Mean age was 36 ± 17 years. Compared to survivors, non-survivors demonstrated significantly higher age, heart rate, diastolic blood pressure, blood glucose, rates of headache, neurological deficits, cognitive dysfunction, impaired consciousness, hydrocephalus, and basal meningeal inflammation. This group also exhibited significantly lower Glasgow Coma Scale (GCS) scores, blood potassium, albumin, and cerebrospinal fluid chloride. Multivariate analysis revealed age (OR 1.042; 95% CI 1.015-1.070; P = 0.002), GCS score (OR 0.693; 95% CI 0.589-0.814; P < 0.001), neurological deficits (OR 5.204; 95% CI 2.056-13.174; P < 0.001), and hydrocephalus (OR 2.680; 95% CI 1.081-6.643; P = 0.033) as independent mortality risk factors. The ROC curve area under age was 0.613 (95% CI 0.506-0.720; P = 0.036) and 0.721 (95% CI 0.615-0.826; P < 0.001) under GCS score. CONCLUSION: Advanced age, reduced GCS scores, neurological deficits, and hydrocephalus were identified as independent risk factors for mortality in stage II and III TBM patients.


Assuntos
Tuberculose Meníngea , Humanos , Masculino , Tuberculose Meníngea/mortalidade , Tuberculose Meníngea/complicações , Feminino , Adulto , Fatores de Risco , Estudos Retrospectivos , Pessoa de Meia-Idade , Adulto Jovem , China/epidemiologia , Escala de Coma de Glasgow , Adolescente
4.
Heliyon ; 10(12): e32887, 2024 Jun 30.
Artigo em Inglês | MEDLINE | ID: mdl-38988586

RESUMO

Dry age-related macular degeneration (AMD) is one of the main diseases that causes blindness in humans, and the number of cases is increasing yearly. However, effective treatments are unavailable, and arbutin (ARB) has been reported to have antioxidant, anti-inflammatory, and anti-aging effects in other age-related diseases. However, whether ARB can be used to treat dry AMD remains unknown. To explore the therapeutic potential and molecular mechanism of arbutin in the treatment of dry AMD. MTT assays, reactive oxygen species (ROS) production assays, flow cytometry assays, qPCR and western blotting were used to assess the impact of ARB on human RPECs induced by H2O2. A transcriptome sequencing assay was used to further explore how ARB acts on human RPECs treated with H2O2. Hematoxylin and eosin (H&E) staining and total antioxidant capacity (T-AOC) assays were used to observe the impact of ARB on mouse retina induced by sodium iodate. ARB counteracted the H2O2-induced reduction in human RPECs viability, ARB reversed H2O2-induced cellular ROS production by increasing the expression of antioxidant-related genes and proteins, ARB also reversed H2O2-induced cell apoptosis by altering the expression of apoptosis-related genes and proteins. Transcriptome sequencing and western blotting showed that ARB reduced ERK1/2 and P-38 phosphorylation to prevent H2O2-induced oxidation damage. The in vivo experiments demonstrated that ARB protected against retinal morphology injury in mice, increased serum T-AOC levels and increased antioxidant oxidase gene expression levels in the mouse retina induced by sodium iodate. We concluded that ARB reversed the H2O2-induced decrease in human RPECs viability through the inhibition of ROS production and apoptosis. The ERK1/2 and P38 MAPK signaling pathways may mediate this process. ARB maintained retinal morphology, increased serum T-AOC level and improved the expression of antioxidant oxidase genes in mice.

5.
Neurosurg Rev ; 47(1): 315, 2024 Jul 12.
Artigo em Inglês | MEDLINE | ID: mdl-38992256

RESUMO

Previous research have demonstrated that the stress hyperglycemia ratio (SHR) accurately reflects acute hyperglycemic states and correlates with adverse outcomes. This study aims to explore the relationship between SHR and the prognosis of patients with aneurysmal subarachnoid hemorrhage (aSAH). Patients with aSAH were categorized into four groups based on SHR tertiles. Functional outcomes were evaluated at 12 months using the modified Rankin Scale (mRS), with scores ranging from 0 to 2 indicating a good outcome and 3-6 indicating a poor outcome. The associations between SHR and functional outcomes were analyzed using logistic regression models and restricted cubic spline analysis. A total of 127 patients exhibited poor functional outcomes. Following comprehensive adjustments, those in the highest SHR tertile had a significantly increased risk of poor prognosis compared to those in the lowest tertile (odds ratio [OR], 4.12; 95% confidence interval [CI]: 1.87-9.06). Moreover, each unit increase in SHR was associated with a 7.51-fold increase in the risk of poor prognosis (OR, 7.51; 95% CI: 3.19-17.70). Further analysis using restricted cubic spline confirmed a linear correlation between SHR and poor prognosis (P for nonlinearity = 0.609). Similar patterns were observed across all studied subgroups. Elevated SHR significantly correlates with poor functional prognosis at one year in patients with aSAH, independent of their diabetes status.


Assuntos
Hiperglicemia , Hemorragia Subaracnóidea , Humanos , Hemorragia Subaracnóidea/complicações , Masculino , Feminino , Pessoa de Meia-Idade , Hiperglicemia/complicações , Prognóstico , Estudos Retrospectivos , Idoso , Adulto , Glicemia
6.
ACS Nano ; 2024 Jul 12.
Artigo em Inglês | MEDLINE | ID: mdl-38993077

RESUMO

Vanadium redox flow battery (VRFB) has garnered significant attention due to its potential for facilitating the cost-effective utilization of renewable energy and large-scale power storage. However, the limited electrochemical activity of the electrode in vanadium redox reactions poses a challenge in achieving a high-performance VRFB. Consequently, there is a pressing need to assess advancements in electrodes to inspire innovative approaches for enhancing electrode structure and composition. This work categorizes three-dimensional (3D) electrodes derived from materials such as foam, biomass, and electrospun fibers. By employing a flexible electrode design and compositional functionalization, high-speed mass transfer channels and abundant active sites for vanadium redox reactions can be created. Furthermore, the incorporation of 3D electrocatalysts into the electrodes is discussed, including metal-based, carbon-based, and composite materials. The strong interaction and ordered arrangement of these nanocomposites have an influence on the uniformity and stability of the surface charge distribution, thereby enhancing the electrochemical performance of the composite electrodes. Finally, the challenges and perspectives of VRFB are explored through advancements in 3D electrodes, 3D electrocatalysts, and mechanisms. It is hoped that this review will inspire the development of methodology and concept of 3D electrodes in VRFB, so as to promote the future development of scientific energy storage and conversion technology.

7.
World J Diabetes ; 15(6): 1254-1262, 2024 Jun 15.
Artigo em Inglês | MEDLINE | ID: mdl-38983810

RESUMO

BACKGROUND: The FreeStyle Libre flash glucose monitoring (FGM) system entered the Chinese market in 2017 to complement the self-monitoring of blood glucose. Due to its increased usage in clinics, the number of studies investigating its accuracy has increased. However, its accuracy has not been investigated in highland popu-lations in China. AIM: To evaluate measurements recorded using the FreeStyle Libre FGM system compared with capillary blood glucose measured using the enzyme electrode method in patients with type 2 diabetes (T2D) who had migrated within 3 mo from highlands to plains. METHODS: Overall, 68 patients with T2D, selected from those who had recently migrated from highlands to plains (within 3 mo), were hospitalized at the Department of Endocrinology from August to October 2017 and underwent continuous glucose monitoring (CGM) with the FreeStyle Libre FGM system for 14 d. Throughout the study period, fingertip capillary blood glucose was measured daily using the enzyme electrode method (Super GL, China), and blood glucose levels were read from the scanning probe during fasting and 2 h after all three meals. Moreover, the time interval between reading the data from the scanning probe and collecting fingertip capillary blood was controlled to < 5 min. The accuracy of the FGM system was evaluated according to the CGM guidelines. Subsequently, the factors influencing the mean absolute relative difference (MARD) of this system were analyzed by a multiple linear regression method. RESULTS: Pearson's correlation analysis showed that the fingertip and scanned glucose levels were positively correlated (R = 0.86, P = 0.00). The aggregated MARD of scanned glucose was 14.28 ± 13.40%. Parker's error analysis showed that 99.30% of the data pairs were located in areas A and B. According to the probe wear time of the FreeStyle Libre FGM system, MARD1 d and MARD2-14 d were 16.55% and 14.35%, respectively (t = 1.23, P = 0.22). Multiple stepwise regression analysis showed that MARD did not correlate with blood glucose when the largest amplitude of glycemic excursion (LAGE) was < 5.80 mmol/L but negatively correlated with blood glucose when the LAGE was ≥ 5.80 mmol/L. CONCLUSION: The FreeStyle Libre FGM system has good accuracy in patients with T2D who had recently migrated from highlands to plains. This system might be ideal for avoiding the effects of high hematocrit on blood glucose monitoring in populations that recently migrated to plains. MARD is mainly influenced by glucose levels and fluctuations, and the accuracy of the system is higher when the blood glucose fluctuation is small. In case of higher blood glucose level fluctuations, deviation in the scanned glucose levels is the highest at extremely low blood glucose levels.

8.
J Hazard Mater ; 476: 135114, 2024 Jul 06.
Artigo em Inglês | MEDLINE | ID: mdl-38986414

RESUMO

Toxicity identification plays a key role in maintaining human health, as it can alert humans to the potential hazards caused by long-term exposure to a wide variety of chemical compounds. Experimental methods for determining toxicity are time-consuming, and costly, while computational methods offer an alternative for the early identification of toxicity. For example, some classical ML and DL methods, which demonstrate excellent performance in toxicity prediction. However, these methods also have some defects, such as over-reliance on artificial features and easy overfitting, etc. Proposing novel models with superior prediction performance is still an urgent task. In this study, we propose a motifs-level graph-based multi-view pretraining language model, called 3MTox, for toxicity identification. The 3MTox model uses Bidirectional Encoder Representations from Transformers (BERT) as the backbone framework, and a motif graph as input. The results of extensive experiments showed that our 3MTox model achieved state-of-the-art performance on toxicity benchmark datasets and outperformed the baseline models considered. In addition, the interpretability of the model ensures that the it can quickly and accurately identify toxicity sites in a given molecule, thereby contributing to the determination of the status of toxicity and associated analyses. We think that the 3MTox model is among the most promising tools that are currently available for toxicity identification.

9.
Nat Aging ; 2024 Jul 10.
Artigo em Inglês | MEDLINE | ID: mdl-38987646

RESUMO

Emerging evidence suggests that neurological and other post-acute sequelae of COVID-19 can persist beyond or develop following SARS-CoV-2 infection. However, the long-term trajectories of cognitive change after a COVID-19 infection remain unclear. Here we investigated cognitive changes over a period of 2.5 years among 1,245 individuals aged 60 years or older who survived infection with the original SARS-CoV-2 strain in Wuhan, China, and 358 uninfected spouses. We show that the overall incidence of cognitive impairment among older COVID-19 survivors was 19.1% at 2.5 years after infection and hospitalization, evaluated using the Telephone Interview for Cognitive Status-40. Cognitive decline primarily manifested in individuals with severe COVID-19 during the initial year of infection, after which the rate of decline decelerated. Severe COVID-19, cognitive impairment at 6 months and hypertension were associated with long-term cognitive decline. These findings reveal the long-term cognitive trajectory of the disease and underscore the importance of post-infection cognitive care for COVID-19 survivors.

10.
Schizophr Res ; 270: 459-464, 2024 Jul 11.
Artigo em Inglês | MEDLINE | ID: mdl-38996523

RESUMO

BACKGROUND: Recent operational criteria for treatment-resistant schizophrenia (TRS) recognized positive and negative symptoms. TRS patients may have heterogeneity in negative symptoms, but empirical data were lacking. We aimed to characterize TRS patients based on negative symptoms using cluster analysis, and to examine between-cluster differences in social functioning. METHODS: We administered the Clinical Assessment Interview of Negative symptoms (CAINS), Brief Negative Symptom Scale (BNSS), the Positive and Negative Syndrome Scale (PANSS) and the Social and Occupational Functional Assessment (SOFAS to 126 TRS outpatients. All patients also completed the Temporal Experience of Pleasure Scale (TEPS), the Emotion Expressivity Scale (EES), and the Social Functional Scale (SFS). A two-stage hierarchical cluster analysis was performed with the CAINS, TEPS and EES as clustering variables. We validated the clusters using ANOVAs to compare group differences in the BNSS, PANSS, SOFAS and SFS. RESULTS: Clustering indices supported a 3-cluster solution. Clusters 1 (n = 46) and 3 (n = 16) exhibited higher CAINS scores than Cluster 2 (n = 64), and were negative-symptom TRS subtypes. Cluster 1 reported lower TEPS than Cluster 3; but Cluster 3 reported lower EES than Cluster 1. Upon validation, Clusters 1 and 3 exhibited higher BNSS scores than Cluster 2, but only Cluster 1 exhibited lower SOFAS and higher PANSS general symptoms than Cluster 2. Both Clusters 1 and 3 had higher self-report functioning than Cluster 2. CONCLUSION: We provided evidence for heterogeneity of negative symptoms in TRS. Negative symptoms can characterize TRS patients and predict functional outcome.

11.
Small ; : e2400496, 2024 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-38949033

RESUMO

Vanadium redox flow battery (VRFB) is a type of energy storage device known for its large-scale capacity, long-term durability, and high-level safety. It serves as an effective solution to address the instability and intermittency of renewable energy sources. Carbon-based materials are widely used as VRFB electrodes due to cost-effectiveness and well-stability. However, pristine electrodes need proper modification to overcome original poor hydrophilicity and fewer reaction active sites. Adjusting the carbon structure is recognized as a viable method to boost the electrochemical activity of electrodes. This review delves into the advancements in research related to ordered and disordered carbon structure electrodes including the adjusting methods, structural characteristics, and catalytic properties. Ordered carbon structures are categorized into nanoscale and macroscale orderliness based on size, leading to improved conductivity and overall performance of the electrode. Disordered carbon structures encompass methods such as doping atoms, grafting functional groups, and creating engineered holes to enhance active sites and hydrophilicity. Based on the current research findings on carbon electrode structures, this work puts forth some promising prospects for future feasibility.

12.
Artigo em Inglês | MEDLINE | ID: mdl-38949761

RESUMO

BACKGROUND: Sjogren's Syndrome (SS) plays important roles in the development of essential hypertension. Nevertheless, with the limitation of reverse causality and confounder in observational studies, such a relationship remains unclear. We aimed to assess the causal relationship of SS and hypertension by the Mendelian randomization (MR) approach. METHODS: We used MR to investigate a causal association between SS and essential hypertension. Inverse variance weighted (IVW), MR Egger regression, Maximum likelihood, Weighted median, and MR pleiotropy residual sum and outlier test (MR-PRESSO) were used in this MR analysis. RESULTS: In this study, we found that the ratio of IVW is 1.00024 (95% CI: 1.00013- 1.00036, P=0.0387), This result was also confirmed by sensitivity analysis methods such as Maximum likelihood is 1.00025 (95% CI: 1.00013-1.00037, P=0.036), MR Egger is 1.00071 (95% CI: 1.00047-1.00095, P=0.0045), and Weighted median is 1.00040 (95% CI: 1.00021- 1.00059, P=0.0322). And MR-Egger intercept method revealed the absence of horizontal pleiotropy in this investigation (P>0.05). The Cochran's Q Test indicated an absence of heterogeneity among them (P>0.05). Heterogeneity and horizontal pleiotropy tests further demonstrate that the results of MR are relatively stable. The above results all suggest that pSS may promote the risk of hypertension. CONCLUSIONS: Our study provides evidence of a causal relationship of SS and hypertension. It is suggested to pay attention to early screening for hypertension, reduce disability and mortality rates, and improve patient prognosis in patients with SS.

13.
Glob Health Med ; 6(3): 212-217, 2024 Jun 30.
Artigo em Inglês | MEDLINE | ID: mdl-38947411

RESUMO

Lacking of adequate knowledge is an obstacle to effective prevention of cervical cancer, yet factors that affect the information acquisition and seeking behavior as well as the information communication process are not well studied. We assessed information acquisition and seeking behavior, as well as perceived barriers of doctor-patient communication regarding human papilloma virus (HPV)-related information of infected women. Among 437 participants, 405 (93%) expressed demands for HPV-related information, while only a small proportion (100/437, 22.9%) actively sought information and felt obstacles comprehending. Web-based channels were most frequently utilized and medical personnel were the most trusted information source. Patients' satisfaction was significantly correlated with doctor's patience (r = 0.581, p < 0.001) and emotional caring (r = 0.555, p < 0.001). Compared to patients not actively seeking information, those actively seeking information were more likely to be single (p = 0.005), had higher education (p = 0.009) and monthly individual-level income (p = 0.023), and was more likely to undergo regular cervical cancer screening (p = 0.003), and were already or willing to be vaccinated (p = 0.008). The actively seeking information group also achieved higher scores in HPV knowledge test (p = 0.007). Public health interventions targeting HPV-infected women using specifically designed educational materials may influence information seeking behavior, increase HPV literacy and knowledge, which could potentially increase HPV vaccine uptake and cervical cancer screening rate.

14.
ACS Omega ; 9(25): 27222-27231, 2024 Jun 25.
Artigo em Inglês | MEDLINE | ID: mdl-38947809

RESUMO

Chromogenic smart windows are one of the key components in improving the building energy efficiency. By simulation of the three-dimensional network of polymer hydrogels, thermal-responsive phase change materials (TRPCMs) are manufactured for energy-saving windows. For simulated polymer hydrogels, tetradecanol (TD) and a color changing dye (CCD) are filled in situ in poly(n-butyl isobutyrate) (PBB) networks. TRPCMs convert solar energy into thermal energy through a dark blue CCD. The TD phase change material (PCM) absorbs heat energy to become a transparent liquid. Simultaneously, the CCD changes from blue to colorless and transparent at around 45 °C. As a result, as-prepared TRPCMs transform from an opaque state at room temperature to a high-transparency state after melting (74.5%). TRPCMs also show a good thermal storage capacity, with a phase transition enthalpy exceeding 161.9 J g-1. As-prepared smart materials can simultaneously achieve photothermal conversion, thermal energy diffusion, latent heat storage, and resistance to liquid leakage at the phase interface between opaque and transparent states, providing more options for the design of energy-saving buildings.

15.
Front Plant Sci ; 15: 1431097, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38947949

RESUMO

Tender bamboo shoots undergo rapid senescence that influences their quality and commercial value after harvest. In this study, the tender sweet bamboo shoots ('Wensun') were packed by a passive modified atmosphere packaging (PMAP) to inhibit the senescence process, taking polyethylene package as control. The increase in CO2 and the decrease in O2 gas concentrations in the headspace atmosphere of the packages were remarkably modified by PMAP treatments. The modified gas atmosphere packaging inhibited the changes in firmness, as well as the content of cellulose, total pectin, and lignin in the cell walls of bamboo shoots. The enzymatic activities of cellulase, pectinase, and polygalacturonase that act on cell wall polysaccharides, and phenylalanine ammonia lyase, cinnamyl alcohol dehydrogenase, peroxidase, and laccase regulating the lignin biosynthesis were modified by PMAP treatment different from control during storage. The expression levels of the lignin biosynthesis genes PePAL3/4, PeCAD, Pe4CL5, PeC4H, PeCCOAOMT, PeCOMT, cellulose synthase PeCESA1, and related transcription factors PeSND2, PeKNAT7, PeMYB20, PeMYB63, and PeMYB85 were clearly regulated. These results suggest that PMAP efficiently retards the changes in lignin and cell wall polysaccharides, thus delaying the senescence of tender sweet bamboo shoots during storage.

16.
J Appl Toxicol ; 2024 Jul 08.
Artigo em Inglês | MEDLINE | ID: mdl-38977376

RESUMO

The (diphtheria, tetanus, and pertussis [acellular, component] [DTacP]) vaccine is a combined vaccine designed to prevent three potentially fatal diseases including pertussis, tetanus, and diphtheria in both children and adults. We utilized advanced technology to develop a novel DTacP vaccine that was previously unavailable in China. The nonclinical studies were performed to evaluate the immunogenicity, potential toxicity, and local tolerance of the vaccine in animal models. In the immunogenicity study, three batches of the vaccine were intraperitoneally administered to National Institutes of Health (NIH) mice, resulting in 100% seropositivity for all three batches. Additionally, antibody levels notably increased as the immunization dosage increased. In acute toxicity study, no mortality was observed among the animals during the 14-day observation period, and no abnormalities in clinical signs were reported. Active systemic anaphylaxis assessment in guinea pigs showed no evidence of serious allergic reactions in the vaccine groups. In the repeat-dose toxicity study, where five intramuscular doses were administered every 2 weeks, gross autopsy and histopathological examination revealed no vaccine-related systemic pathological changes in rats, with dose site irritant reactions mostly recovered at the end of recovery period. In conclusion, the vaccine demonstrated good local and systemic tolerance, supporting its clinical development.

18.
J Leukoc Biol ; 2024 Jul 16.
Artigo em Inglês | MEDLINE | ID: mdl-39012079

RESUMO

Although tumor cell-derived microparticles (MPs) vaccines have reportedly induced anti-tumor immune reactions for various cancers, the mechanism by which MPs derived from Hepa1-6 cells are taken up by dendritic cells (DCs) and provide the MPs antigens message to CD8+ T cells to exert their anti-hepatocellular carcinoma (HCC) effects remain unclear. Furthermore, the role of MPs in combination with the small-molecule drug MSI-1436, an inhibitor of protein tyrosine phosphatase 1B (PTP1B), in HCC has not yet been reported. In this study, protein mass spectrometry combined with cytology revealed that MPs are mainly taken up by DCs via the clathrin-mediated endocytosis and phagocytosis pathway and localized mainly in lysosomes. High concentration of tumor necrosis factor (TNF)-α and interferon (IFN)-γ were detected in CD8+ T cells stimulated with MPs-loaded DCs. Moreover, MPs combined with MSI-1436 further suppressed the proliferation of HCC cells in C57BL/6 tumor-bearing mice, which was closely correlated with CD4+/CD8+ T cells counts in peripheral blood, spleen, and the tumor microenvironment. Mechanistically, the combination of MPs and MSI-1436 exerts a more powerful anti-HCC effect, which may be related to the further inhibition of the expression of PTP1B. Overall, MPs combined with MSI-1436 exerted stronger anti-tumor effects than MPs or MSI-1436 alone. Therefore, the combination of MPs and MSI-1436 may be a promising means of treating HCC.

19.
Cell Rep ; 43(7): 114505, 2024 Jul 11.
Artigo em Inglês | MEDLINE | ID: mdl-39002128

RESUMO

Increasing global concerns about psychoactive substance addiction and psychotic disorders highlight the need for comprehensive research into the structure-function relationship governing ligand recognition between these substances and their receptors in the brain. Recent studies indicate the significant involvement of trace amine-associated receptor 1 (TAAR1) in the signaling regulation of the hallucinogen lysergic acid diethylamide (LSD) and other antipsychotic drugs. This study presents structures of the TAAR1-Gs protein complex recognizing LSD, which exhibits a polypharmacological profile, and the partial agonist RO5263397, which is a drug candidate for schizophrenia and addiction. Moreover, we elucidate the cross-species recognition and partial activation mechanism for TAAR1, which holds promising implications from a drug discovery perspective. Through mutagenesis, functional studies, and molecular dynamics (MD) simulations, we provide a comprehensive understanding of a versatile TAAR1 pocket in recognizing various ligands as well as in the ligand-free state, underpinning the structural basis of its high adaptability. These findings offer valuable insights for the design of antipsychotic drugs.

20.
Neoplasma ; 71(3): 243-254, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38958714

RESUMO

Allicin (AL) is one of garlic-derived organosulfides and has a variety of pharmacological effects. Studies have reported that AL has notable inhibitory effects on liver cancer, gastric cancer, breast cancer, and other cancers. However, there are no relevant reports about its role in human nasopharyngeal carcinoma. Ferroptosis is an iron-dependent form of non-apoptotic regulated cell death. Increasing evidence indicates that induction of ferroptosis can inhibit the proliferation, migration, invasion, and survival of various cancer cells, which act as a tumor suppressor in cancer. In this study, we confirmed that AL can inhibit cell proliferation, migration, invasion, and survival in human nasopharyngeal carcinoma cells. Our finding shows that AL can induce the ferroptosis axis by decreasing the level of GSH and GPX4 and promoting the induction of toxic LPO and ROS. AL-mediated cytotoxicity in human nasopharyngeal carcinoma cells is dependent on ferroptosis. Therefore, AL has good anti-cancer properties and is expected to be a potential drug for the treatment of nasopharyngeal carcinoma.


Assuntos
Proliferação de Células , Dissulfetos , Ferroptose , Carcinoma Nasofaríngeo , Neoplasias Nasofaríngeas , Espécies Reativas de Oxigênio , Ácidos Sulfínicos , Humanos , Ferroptose/efeitos dos fármacos , Dissulfetos/farmacologia , Carcinoma Nasofaríngeo/tratamento farmacológico , Carcinoma Nasofaríngeo/patologia , Proliferação de Células/efeitos dos fármacos , Ácidos Sulfínicos/farmacologia , Neoplasias Nasofaríngeas/tratamento farmacológico , Neoplasias Nasofaríngeas/patologia , Linhagem Celular Tumoral , Espécies Reativas de Oxigênio/metabolismo , Movimento Celular/efeitos dos fármacos , Fosfolipídeo Hidroperóxido Glutationa Peroxidase/metabolismo , Glutationa/metabolismo , Sobrevivência Celular/efeitos dos fármacos
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