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1.
Heart Lung ; 69: 71-77, 2024 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-39357290

RESUMO

BACKGROUND: Many studies have reported correlations between diet-derived antioxidants and asthma. Nevertheless, the probable association between diet-derived antioxidants and asthma remains a matter of discussion. OBJECTIVES: We explored the association between Diet-Derived Antioxidants and Asthma. METHODS: We used data from the 2003-2018 National Health and Nutrition Examination Survey (NHANES) to assess the relationship between diet-derived antioxidants and asthma and a two-sample Mendelian randomization (MR) study was employed to assess the causal associations between lifelong diet-derived circulating antioxidant levels and the risk of asthma. RESULTS: Participants with asthma were more likely to be young-to-middle-aged females, smokers, have lower income, belong to non-Hispanic Black ethnicity, have a high school education, have a BMI over 30. The dietary intakes of vitamin C, zinc, selenium, and CDAI were negatively associated with asthma risk (Vitamin C: OR = 0.76, 95 % CI: 0.63-0.91, P = 0.032; Zinc: OR = 0.86, 95 % CI: 0.75-1.00, P = 0.046; Selenium: OR = 0.85, 95 % CI: 0.73-0.98, P = 0.004; CDAI: OR = 0.80, 95 % CI: 0.65-0.97, P = 0.027). There was a significant nonlinear relationship between the dietary intake of vitamin C, zinc, and selenium and the risk of asthma (Pnon-linear < 0.05). However, no causal link between circulating antioxidants and asthma risk was found in the MR analysis. Sensitivity analyses supported the robustness of the results. CONCLUSION: In the observational study, we identified a negative correlation between the dietary intake of vitamin C, zinc, selenium, and CDAI and asthma risk, while our MR analyses did not find evidence to support a causal relationship between diet-derived antioxidants and the risk of asthma.

2.
bioRxiv ; 2024 Sep 23.
Artigo em Inglês | MEDLINE | ID: mdl-39372772

RESUMO

"GABA dysfunction" is a major hypothesis for the biological basis of schizophrenia with indirect supporting evidence from human post-mortem brain and genetic studies. Patient-derived induced pluripotent stem cells (iPSCs) have emerged as a valuable platform for modeling psychiatric disorders, and previous modeling has revealed glutamatergic synapse deficits. Whether GABAergic synapse properties are affected in patient-derived human neurons and how this impacts neuronal network activity remain poorly understood. Here we optimized a protocol to differentiate iPSCs into highly enriched ganglionic eminence-like neural progenitors and GABAergic neurons. Using a collection of iPSCs derived from patients of psychiatric disorders carrying a Disrupted-in-Schizophrenia 1 ( DISC1 ) mutation and their unaffected family member, together with respective isogenic lines, we identified mutation-dependent deficits in GABAergic synapse formation and function, a phenotype similar to that of mutant glutamatergic neurons. However, mutant glutamatergic and GABAergic neurons contribute differentially to neuronal network excitability and synchrony deficits. Finally, we showed that GABAergic synaptic transmission is also defective in neurons derived from several idiopathic schizophrenia patient iPSCs. Transcriptome analysis further showed some shared gene expression dysregulation, which is more prominent in DISC1 mutant neurons. Together, our study supports a functional GABAergic synaptic deficit in major psychiatric disorders.

3.
Mater Horiz ; 2024 Oct 04.
Artigo em Inglês | MEDLINE | ID: mdl-39364564

RESUMO

Flexible dual mode strain-temperature sensors that mimic human skin functions are highly desired for wearable devices and intelligent robots. However, integrating dual sensing characteristics into a single sensor for simultaneous and decoupled strain-temperature detection still remains a challenge. Herein, we report a flexible dual-modal sensor that uses a "neutral surface" structural design technique to integrate an independently prepared temperature sensing layer (TSL) and strain sensing layer (SSL), for simultaneous monitoring of strain and temperature, in a decoupled manner. The TSL consists of a PDMS/BaTiO3 based dielectric layer whose dielectric constant and thickness change in response to temperature fluctuations. The SSL consists of a resistive type Ni80Cr20 film whose resistance changes in response to external strain. After optimizing the temperature and strain sensing characteristics of the TSL and SSL, the obtained dual-modal flexible sensor has shown a broad temperature sensing range (30 to 200 °C), with high temperature sensitivity (-160.90 fF °C-1), excellent linearity (0.998), and highly discernible temperature resolution (0.1 °C). Additionally, the sensor has also exhibited a wide strain monitoring range (20 to 1000 µÎµ), good strain resolution (20 µÎµ or 0.002%), and a fast strain response time (54 ms). When practically demonstrated, our sensor has successfully shown independent perception of strain and temperature, which highlights its promising application potential in the fields of smart robotics and intelligent prosthetics.

4.
Front Public Health ; 12: 1446295, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-39421821

RESUMO

Background: With the intensification of the global aging trend, there is a contradiction between the extended lifespan and the decline of physiological functions among the older adult. It has become a global consensus to focus on and improve the quality of life for the older adult. Mind-body exercises (Tai Chi, Ba Duan Jin, Yi Jin Jing) play a crucial role in promoting the quality of life for older adults, but the mechanisms and mediating effects are not yet clear. Objective: This study examines the impact of mind-body exercises (Tai Chi, Ba Duan Jin, Yi Jin Jing) on the quality of life in older adults, with a particular focus on exploring the chain mediating effects of perceived social support and psychological resilience. Methods: This study is a cross-sectional study that surveyed 1,087 older adults participating in mind-body exercises (Tai Chi, Ba Duan Jin, Yi Jin Jing) in 13 districts of Beijing, China, from March 25 to May 3, 2024. The Physical Activity Rating Scale (PARS-3), the World Health Organization Quality of Life Scale (WHOQOL-BREF), the Perceived Social Support Scale (PSSS), and the Connor-Davidson Resilience Scale (CD-RISC) were used to measure mind-body exercise, perceived social support, psychological resilience, and quality of life, respectively. Data were statistically analyzed using SPSS 26.0, and mediation effects were tested and effect analysis was conducted through structural equation modeling (AMOS) and the Bootstrap method. Results: The study results show that mind-body exercises (Tai Chi, Ba Duan Jin, Yi Jin Jing) are significantly and positively correlated with the quality of life in older adults (r = 0.549, p < 0.01). The path coefficients for the relationships mind-body exercise → perceived social support (ß = 0.46, p < 0.001) → psychological resilience (ß = 0.20, p < 0.001) → quality of life in older adults (ß = 0.39, p < 0.001) are significant, indicating that perceived social support and psychological resilience have a chain mediating effect between mind-body exercise and the quality of life in older adults. Conclusion: Mind-body exercises not only improve the quality of life for older adults but also indirectly enhance it by strengthening perceived social support and psychological resilience. This study provides significant reference for developing health intervention strategies targeted at older adults, suggesting that promoting mind-body exercises can improve their sense of perceived social support and psychological resilience, thereby increasing their quality of life.


Assuntos
Qualidade de Vida , Resiliência Psicológica , Apoio Social , Tai Chi Chuan , Humanos , Qualidade de Vida/psicologia , Idoso , Masculino , Feminino , Estudos Transversais , Tai Chi Chuan/psicologia , China , Inquéritos e Questionários , Pessoa de Meia-Idade , Idoso de 80 Anos ou mais , Exercício Físico/psicologia , Terapias Mente-Corpo
5.
Asia Pac J Ophthalmol (Phila) ; : 100098, 2024 Oct 02.
Artigo em Inglês | MEDLINE | ID: mdl-39366638

RESUMO

PURPOSE: The objective of this paper is to shed light on the current landscape of genotyping practices, phenotyping practices and availability of essential vision rehabilitation management for inherited retinal diseases (IRD) in the Asia-Pacific (APAC) Region. METHODS: The 62-item questionnaire was distributed electronically via email. The questions covered five domains: (1) structure of the IRD service and registry/database; (2) genotyping practices; (3) genetic counselling; (4) deep phenotyping practices; (5) low-vision rehabilitation services. RESULTS: The survey was completed by 36 of 45 centres in twelve countries and regions in APAC. Among these centres, 42 % reported managing more than 1000 patients. Notably, 39 % of centres lack an IRD database or registry, and 44 % of centres have tested less than one-quarter of their IRD patients. The majority of centres (67 %) do not have genetic counsellors. While there was consistency in the imaging-based investigations, there was marked heterogeneity for functional testing using electrophysiology and formal perimetry. Only 34 % of centres confirmed the availability of access to low-vision assistive devices. CONCLUSIONS: This study reveals several critical gaps in managing IRDs in the APAC region. These include the lack of IRD database/registry in one-third of centres, a substantial proportion of patients remaining genetically undiagnosed, and limited availability of genetic counsellors. The findings also underscore a need to harmonise investigations for evaluating retinal function and identify areas for improvement in the provision of low-vision rehabilitation services.

6.
Small Methods ; : e2400904, 2024 Oct 21.
Artigo em Inglês | MEDLINE | ID: mdl-39428866

RESUMO

Hepatocellular carcinoma (HCC) is typically characterized by rich vascularity, with angiogenesis playing a crucial role in its growth and invasion. Molecular imaging of specific receptors in blood vessels is crucial in HCC diagnosis. In particular, in vivo imaging utilizing the second near-infrared (NIR-II) window offers improved tissue penetration, reduced light scattering, and lower autofluorescence. Despite the great potential of the NIR-II window, developing safe and effective probes to provide better imaging performance for HCC is urgently needed. In this study, NIR-II imaging integrated with a vascular endothelial growth factor receptor (VEGFR)-targeted probe generated by combining a VEGFR-targeted peptide with indocyanine green (ICG) is used to characterize HCC-related angiogenesis at a resolution of 56.0 µm. For the first time, liver metabolic curves and parameters of liver function reserve (LFR) are obtained by fitting NIR-II fluorescence signals with high spatiotemporal resolution, showing significant differences between HCC mice and controls. Moreover, unlike ICG, the targeting probe has a targeted effect on blood vessels in vivo. The tumor-to-normal (T/N) ratio in NIR-II imaging reaches up to 3.30 after post-injection of the targeting probe. The results indicate that the VEGFR-targeted probe is a powerful tool for NIR-II fluorescence imaging to enhance early diagnosis of HCC.

7.
Acta Pharm Sin B ; 14(9): 4118-4133, 2024 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-39309507

RESUMO

The immunosuppressive phenotype of tumor cells extensively attenuates the immune activation effects of traditional treatments. In this work, a transferrin receptor (TfR) targeted immunostimulant (PTI) is fabricated for photodynamic immunotherapy against metastatic tumors by interrupting ß-catenin signal pathway. To synthesize PTI, the photosensitizer conjugated TfR targeting peptide moiety (Palmitic-K(PpIX)-HAIYPRH) is unitized to encapsulate the transcription interrupter of ICG-001. On the one hand, the recognition of PTI and TfR can promote drug delivery into tumor cells to destruct primary tumors through photodynamic therapy and initiate an immunogenic cell death with the release of tumor-associated antigens. On the other hand, PTI will interrupt the binding between ß-catenin and cAMP response element-binding protein (CREB), regulating the gene transcription to downregulate programmed death ligand 1 (PD-L1) while upregulating C-C motif chemokine ligand 4 (CCL4). Furthermore, the elevated CCL4 can recruit the dendritic cells to present tumor-specific antigens and promote T cells activation and infiltration, and the downregulated PD-L1 can avoid the immune evasion of tumor cells and activate systemic anti-tumor immunity to eradicate lung metastasis. This work may inspire the development of antibody antibody-free strategy to activate systemic immune response in consideration of immunosuppressive conditions.

8.
Curr Drug Deliv ; 2024 Sep 16.
Artigo em Inglês | MEDLINE | ID: mdl-39289947

RESUMO

OBJECTIVE: Hepatocellular carcinoma (HCC) poses a major healthcare burden globally. Traditional Chinese medicine formula Bushen Jianpi (BSJP) recipe shows inhibitory effects on HCC but suffers from low bioavailability. This study aims to develop a BSJP-loaded liposome (BSJP@Lip) for targeted HCC treatment. METHODS: BSJP@Lip was prepared using a microfluidic device. Particle characterization included size, morphology, drug loading, encapsulation efficiency, and release kinetics analysis. In vitro cytotoxicity, cellular uptake, apoptosis, and protein expression were evaluated in hepG2, Smmc-7721, and hepa 1-6 hepatic cancer cell lines treated with BSJP@Lip. RESULTS: BSJP@Lip nanoparticles showed a uniform spherical shape with an average size of 50 nm and zeta potential at around -2.24 mV. They significantly inhibited cell viability and induced apoptosis in a dose-dependent manner compared with traditional decoction formulations. Enhanced cellular uptake of BSJP@Lip increased the expression of proinflammatory factors IL-18 and NLRP3. CONCLUSION: BSJP@Lip nanoparticles were found to be efficiently internalized by hepatic cancer cell lines, resulting in a dose-dependent inhibition of cell viability and induction of apoptosis. This effect was accompanied by the upregulation of IL-18 and NLRP3.

9.
BMJ Open ; 14(9): e079531, 2024 Sep 10.
Artigo em Inglês | MEDLINE | ID: mdl-39260839

RESUMO

OBJECTIVES: This study explored the mechanisms by which physical activity was associated with depressive symptoms in multi-ethnic (Han, Yi and Tibetan) adolescents in southwest China. The mediating role of insomnia in the association of physical activity with depressive symptoms, the moderating role of resilience in this mediation model and the moderating role of parental absence in the moderated mediation model were also examined. DESIGN: A cross-sectional survey. SETTING: In southwest China (Sichuan Province and Tibet Autonomous Region). PARTICIPANTS: 3195 adolescents from a school-based survey conducted between April and October 2020. METHODS: There were 3143 valid samples in this study (47.2% males with mean age=12.88±1.68 years). Structural equation models were developed to estimate the direct and mediating effect, and the moderating effect. Multigroup comparison was performed to examine the differences and similarities of the moderated mediation model across three parental absence subgroups: (1) both parents present, (2) one parent absent and (3) both parents absent. RESULTS: As hypothesised, physical activity was significantly and positively associated with the reduction of depressive symptoms in adolescents. Insomnia partially mediated the effect of physical activity on depressive symptoms. In addition, resilience moderated the direct and indirect effects of physical activity (through insomnia) on depressive symptoms. Finally, the multigroup comparison indicated the moderating effect of parental absence on the moderated mediation model. CONCLUSIONS: Physical activity was associated with alleviating insomnia symptoms among adolescents, thus correlating with the improvement of their depressive symptoms. Resilience was associated with enhancing the beneficial effects of physical activity, further improving depressive symptoms among adolescents, especially those with both absent parents. It is evident that physical activity interventions should be further incorporated into public health programmes to foster the physical and mental health of left-behind adolescents in southwest China.


Assuntos
Depressão , Exercício Físico , Pais , Resiliência Psicológica , Distúrbios do Início e da Manutenção do Sono , Humanos , Masculino , Adolescente , Feminino , Distúrbios do Início e da Manutenção do Sono/psicologia , Distúrbios do Início e da Manutenção do Sono/epidemiologia , Estudos Transversais , Depressão/epidemiologia , Depressão/psicologia , China/epidemiologia , Exercício Físico/psicologia , Pais/psicologia , Criança
10.
Artigo em Inglês | MEDLINE | ID: mdl-39292585

RESUMO

We introduce HOLI-1-to-3, a novel technique for holistic 3D shape recovery from a single-viewpoint input, by effectively combining line-of-sight (LOS) and non-line-of-sight (NLOS) imaging. We leverage advancements in ultrafast time-of-flight (ToF) sensors and learning-based 3D shape inference techniques, such as diffusion models. HOLI-1-to-3 employs a new neural plenoptic representation, which unifies radiance fields (for LOS RGB images) and transient fields (for NLOS transients). HOLI-1-to-3 is optimized through a two-stage pipeline involving diffusion priors and transients prior. Our technique allows for accurate and continuous reconstruction of both visible and invisible parts of objects from a single view. Comprehensive experiments on both simulated and real-world datasets demonstrate the effectiveness of HOLI-1-to-3 in resolving ambiguities in invisible parts of objects and significantly improving overall generation quality. The datasets used in our experiments will be made available to the research community to facilitate further achievements in holistic 3D shape recovery.

11.
J Ethnopharmacol ; 337(Pt 2): 118854, 2024 Sep 24.
Artigo em Inglês | MEDLINE | ID: mdl-39326815

RESUMO

ETHNOPHARMACOLOGICAL RELEVANCE: Saffron is one of the traditional medicinal herbs, which contains various active ingredients, such as safranal, crocin, saffron acid, etc. It has anti-inflammatory, antioxidant, and anti-cancer properties, and is widely used in clinical practice. The anti-cancer efficacy of saffron has been previously confirmed, but its anti-cancer mechanism in colorectal cancer remains unclear. OBJECTIVE: We investigated the effect of active compounds of saffron on the efficacy of immunotherapy for colorectal cancer. METHODS: TCMSP and liquid chromatography-mass spectrometry analysis (LC-MS), GeneCards, and DisGeNET databases were used to identify the active compounds of saffron, drug targets and the disease targets of colorectal cancer. They were then subjected to Gene Ontology Enrichment (GO) and Signalling Pathway Enrichment (KEGG) analyses. The core targets and corresponding compounds were selected for molecular docking. The effect of active components of saffron on the proliferation of CT26 and HCT116 cells was investigated using the cell counting kit-8 (CCK-8). In vitro experiments were conducted by subcutaneous injection of CT26 cells to establish a colon cancer model. Enzyme-linked immunosorbent assay (ELISA), western blotting (WB), real-time polymerase chain reaction (RT-PCR), immunohistochemistry (IHC), and flow cytometry (FCM) were employed to validate the effects of saffron on colorectal cancer immunotherapy. RESULTS: 1. LC-MS analysis revealed that the main active component of saffron extract was crocin. The active chemicals of saffron intersected with 170 colorectal cancer targets, with 17 predicting targets for saffron treatment. GO and KEGG enrichment analyses revealed that the active components of saffron can prevent colorectal cancer development by enhancing Th17 cell differentiation and the IL-17 signaling pathway. 2. In vitro studies revealed that saffron alcohol extract, crocin, and safranal can suppress the proliferation of CT26 and HCT116 cells. 3. In vivo studies showed that crocin and safranal can increase the body mass and decrease the tumor mass of loaded mice, decrease the serum level of IL-17, and lower the mRNA expression level of IL-17, IL-6, TNF-α, TGF-ß, and PD-L1 and IL-17, PD-L1 protein in tumors. This inhibitory effect was strengthened after combined immunotherapy. In addition, saffron modulated CD4+ and CD8+ T cells and the CD4+/CD8+T ratio in mouse spleens. CONCLUSION: The active components of saffron can reduce the expression of inflammatory factors and ameliorate the immunological microenvironment of tumors via the IL-17 signaling pathway, thereby improving the efficacy of immunotherapy for colorectal cancer. This study provides pharmacological support for the application of saffron in enhancing the efficacy of immunotherapy for colorectal cancer.

12.
J Colloid Interface Sci ; 678(Pt C): 841-853, 2024 Sep 21.
Artigo em Inglês | MEDLINE | ID: mdl-39321640

RESUMO

Chemodynamic therapy (CDT) is emerging as a promising treatment for biofilm infections. However, its effectiveness is significantly hindered by several factors: the body's stable temperature, a limited supply of Fe2+ ions, and inadequate endogenous levels of H2O2 at the infection sites. Herin, our study introduces MPN-crosslinked hyaluronic acid (HA) nanogels as an effective strategy for treating biofilm-associated infections. The DHA@HA-TA/Fe (DHTF) nanogel is synthesized through the coordination reaction between Fe2+ ions and tannic acid (TA)-modified HA, with dihydroartemisinin (DHA) encapsulated within the structure. DHTF exhibits pH-/hyaluronidase-responsiveness in the biofilm infection microenvironment, enabling sustained release of DHA as a substitute for H2O2 and Fe2+ for CDT. The incorporation of Fe2+/TA-based MPN and DHA within the nanogels enables photothermal/DHA dually-enhanced CDT, facilitating efficient disruption of biofilm matrices and bacterial eradication through boosting reactive oxygen species production. In vivo studies demonstrate that DHTF exhibit prolonged retention within biofilms. This ensures a sustained release of therapeutic agents and continuous anti-biofilm activity. Eventually, both in vitro and in vivo evaluations consistently confirm the significant anti-biofilm capacity of DHTF. Our findings highlight the potential of DHTF as a promising nanomedicine for biofilm-related infections, offering efficient treatment strategies that could improve clinical management of these challenging conditions.

13.
Endocr Connect ; 13(11)2024 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-39240241

RESUMO

Objective: Hyperthyroidism, a prevalent endocrine disorder, can lead to complications such as liver failure due to the liver's essential role in thyroid hormone metabolism. The study aimed to elucidate the respective contributions of 131I and/or ALSS in managing hyperthyroidism alongside liver failure. Methods: A retrospective analysis was carried out on 74 patients diagnosed with severe liver failure in the context of Graves' disease. Patients were categorized into three groups: group A (n = 34) received 131I treatment, group B (n = 17) underwent 131I and ALSS treatment, and group C (n = 24) received artificial liver support system (ALSS) treatment alone. Results: Throughout the treatment period, the liver function indexes in all groups exhibited a declining trend. The thyroid function of group A and group B treated with 131I was significantly improved compared to that before treatment. There was no significant change in thyroid function in group C. After the correction of hyperthyroidism, significant improvements were observed in the liver function of individuals in groups A and B, particularly with more noticeable amelioration compared to group C. After two months of treatment, the efficacy rates for the three groups were 79.41%, 82.35%, and 60.87% respectively. Mortality rates of the three groups were 5.88%, 17.65%, and 36% (P < 0.01). Group B, receiving both 131I and ALSS treatments, exhibited a lower mortality rate than group C. Conclusion: In cases of severe liver failure accompanied by hyperthyroidism, prompt administration of 131I is recommended to alleviate the adverse effects of hyperthyroidism on liver function and facilitate a conducive environment for the recovery of liver functionality.

14.
Invest Ophthalmol Vis Sci ; 65(10): 5, 2024 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-39093298

RESUMO

Purpose: Retinal neovascularization is a significant feature of advanced age-related macular degeneration (AMD) and a major cause of blindness in patients with AMD. However, the underlying mechanism of this pathological neovascularization remains unknown. Iron metabolism has been implicated in various biological processes. This study was conducted to investigate the effects of iron metabolism on retinal neovascularization in neovascular AMD (nAMD). Methods: C57BL/6J and very low-density lipoprotein receptor (VLDLR) knockout (Vldlr-/-) mice, a murine model of nAMD, were used in this study. Bulk-RNA sequencing was used to identify differentially expressed genes. Western blot analysis was performed to test the expression of proteins. Iron chelator deferiprone (DFP) was administrated to the mice by oral gavage. Fundus fluorescein angiography was used to evaluate retinal vascular leakage. Immunofluorescence staining was used to detect macrophages and iron-related proteins. Results: RNA sequencing (RNA-seq) results showed altered transferrin expression in the retina and RPE of Vldlr-/- mice. Disrupted iron homeostasis was observed in the retina and RPE of Vldlr-/- mice. DFP mitigated iron overload and significantly reduced retinal neovascularization and vascular leakage. In addition, DFP suppressed the inflammation in Vldlr-/- retinas. The reduced signals of macrophages were observed at sites of neovascularization in the retina and RPE of Vldlr-/- mice after DFP treatment. Further, the IL-6/JAK2/STAT3 signaling pathway was activated in the retina and RPE of Vldlr-/- mice and reversed by DFP treatment. Conclusions: Disrupted iron metabolism may contribute to retinal neovascularization in nAMD. Restoring iron homeostasis by DFP could be a potential therapeutic approach for nAMD.


Assuntos
Deferiprona , Modelos Animais de Doenças , Homeostase , Quelantes de Ferro , Ferro , Camundongos Endogâmicos C57BL , Camundongos Knockout , Neovascularização Retiniana , Animais , Deferiprona/farmacologia , Deferiprona/uso terapêutico , Quelantes de Ferro/farmacologia , Quelantes de Ferro/uso terapêutico , Camundongos , Ferro/metabolismo , Neovascularização Retiniana/metabolismo , Neovascularização Retiniana/tratamento farmacológico , Neovascularização Retiniana/etiologia , Neovascularização Retiniana/patologia , Angiofluoresceinografia , Receptores de LDL/genética , Receptores de LDL/metabolismo , Western Blotting , Epitélio Pigmentado da Retina/metabolismo , Epitélio Pigmentado da Retina/efeitos dos fármacos , Epitélio Pigmentado da Retina/patologia , Degeneração Macular Exsudativa/tratamento farmacológico , Degeneração Macular Exsudativa/metabolismo , Fator de Transcrição STAT3/metabolismo , Masculino
15.
J Control Release ; 374: 230-241, 2024 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-39151829

RESUMO

The combination of therapy-induced immunogenic cell death (ICD) and immune checkpoint blockade can provide a mutually reinforced strategy to reverse the poor immunogenicity and immune escape behavior of tumors. In this work, a chimeric peptide-engineered immunostimulant (ER-PPB) is fabricated for endoplasmic reticulum (ER)-targeted photodynamic immunotherapy against metastatic tumors. Among which, the amphiphilic chimeric peptide (ER-PP) is composed of ER-targeting peptide FFKDEL, hydrophilic PEG8 linker and photosensitizer protoporphyrin IX (PpIX), which could be assembled with a PD-1/PD-L1 blocker (BMS-1) to prepare ER-PPB. After passively targeting at tumor tissues, ER-PPB will selectively accumulate in the ER. Next, the localized PDT of ER-PPB will produce a lot of ROS to destroy the primary tumor cells, while increasing the ER stress to initiate a robust ICD cascade. Moreover, the concomitant delivery of BMS-1 can impede the immune escape of tumor cells through PD-1/PD-L1 blockade, thus synergistically activating the immune system to combat metastatic tumors. In vitro and in vivo results demonstrate the robust immune activation and metastatic tumor inhibition characteristics of ER-PPB, which may offer a promising strategy for spatiotemporally controlled metastatic tumor therapy.


Assuntos
Retículo Endoplasmático , Imunoterapia , Peptídeos , Fotoquimioterapia , Fármacos Fotossensibilizantes , Protoporfirinas , Animais , Fotoquimioterapia/métodos , Imunoterapia/métodos , Fármacos Fotossensibilizantes/administração & dosagem , Fármacos Fotossensibilizantes/uso terapêutico , Fármacos Fotossensibilizantes/farmacologia , Linhagem Celular Tumoral , Peptídeos/química , Peptídeos/administração & dosagem , Protoporfirinas/administração & dosagem , Protoporfirinas/química , Humanos , Camundongos , Adjuvantes Imunológicos/administração & dosagem , Adjuvantes Imunológicos/uso terapêutico , Adjuvantes Imunológicos/farmacologia , Feminino , Antígeno B7-H1/antagonistas & inibidores , Antígeno B7-H1/imunologia , Receptor de Morte Celular Programada 1/antagonistas & inibidores , Receptor de Morte Celular Programada 1/imunologia , Camundongos Endogâmicos BALB C , Camundongos Endogâmicos C57BL , Neoplasias/terapia , Neoplasias/imunologia , Neoplasias/patologia , Estresse do Retículo Endoplasmático/efeitos dos fármacos
16.
PeerJ ; 12: e17838, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-39157771

RESUMO

Purpose: The aim of this study was to identify factors associated with difficult video laryngoscopy in obese patients. Methods: A total of 579 obese patients undergoing elective laparoscopic weight loss surgery were intubated with a single-lumen endotracheal tube using a video laryngoscopy under general anesthesia, and the patients were divided into two groups based on the Cormack-Lehane classification (difficult video laryngoscopy defined as ≥ 3): the easy video laryngoscopy group and the difficult video laryngoscopy group. Record the general condition of the patient, bedside testing indicators related to the airway, Cormack-Lehane classification during intubation, and intubation failure rate. Results: The findings of this study show that the incidence of difficult video laryngoscopy in obese patients is 4.8%. Multivariate logistic regression analysis indicated that body mass index was significantly associated with difficult video laryngoscopy (OR = 1.082, 95% CI [1.033-1.132], P < 0.001). Conclusion: For Chinese obese patients without known difficult airways, the incidence of difficult video laryngoscopy is 4.8%. Body mass index is associated factors for the occurrence of difficult video laryngoscopy, with an increased risk observed as body mass index rise.


Assuntos
Índice de Massa Corporal , Intubação Intratraqueal , Laringoscopia , Obesidade , Humanos , Laringoscopia/métodos , Laringoscopia/efeitos adversos , Masculino , Feminino , Estudos Prospectivos , Obesidade/cirurgia , Intubação Intratraqueal/métodos , Intubação Intratraqueal/efeitos adversos , Pessoa de Meia-Idade , Adulto , China/epidemiologia , Laparoscopia/métodos , Fatores de Risco , Cuidados Pré-Operatórios/métodos , Gravação em Vídeo , Anestesia Geral
17.
BMJ Open Ophthalmol ; 9(1)2024 Aug 13.
Artigo em Inglês | MEDLINE | ID: mdl-39142698

RESUMO

AIMS: To explore the sensitive components of full-field electroretinography (ERG) as indicators of retina function at the onset of acute ischaemic central retinal vein occlusion (CRVO). METHODS: 11 patients (11 eyes) with ischaemic CRVO and 32 patients (32 eyes) with non-ischaemic CRVO who presented with first-episode unilateral CRVO within 1 month of symptom onset and with no previous intervention were examined by the International Society for Clinical Electrophysiology of Vision standard ERG. RESULTS: A significant amplitude decline and peak time delay in light-adapted (LA) 3 ERG and LA 30 Hz flicker ERG (p<0.05 for all) was found in the ischaemic CRVO eyes, compared with the non-ischaemic CRVO eyes. The b/a amplitude ratio of dark-adapted (DA) 3 ERG, DA 10 ERG and LA 3 ERG was significantly different between the ischaemic and non-ischaemic groups (p<0.05 for all). Regarding oscillatory potentials (OPs), the amplitudes of OP1, OP2 and OP3 as well as the sum of DA 3 OP1-4 amplitudes (∑OPs) showed significant changes (p<0.01 for all) between two groups. No peak time delay of OPs was found between the ischaemic and non-ischaemic CRVO eyes. CONCLUSION: The amplitude of DA 0.01 ERG, components of LA 3 ERG and LA 30 Hz flicker ERG, and the b/a amplitude ratio could be among the most sensitive indicators in patients with acute ischaemic CRVO. The amplitudes of OP1, OP2, OP3 and ∑OPs in the CRVO eyes were reduced to 40% of the control values, showing that this quantitative method is reliable for detecting ischaemic retinal diseases, even in early stage.


Assuntos
Eletrorretinografia , Isquemia , Retina , Oclusão da Veia Retiniana , Humanos , Oclusão da Veia Retiniana/fisiopatologia , Oclusão da Veia Retiniana/diagnóstico , Eletrorretinografia/métodos , Masculino , Feminino , Pessoa de Meia-Idade , Idoso , Doença Aguda , Isquemia/fisiopatologia , Isquemia/diagnóstico , Retina/fisiopatologia , Retina/diagnóstico por imagem , Acuidade Visual/fisiologia , Adaptação à Escuridão/fisiologia , Adulto
18.
Vet Microbiol ; 296: 110175, 2024 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-39018941

RESUMO

Mycoplasma gallisepticum (MG) is the primary causative agent of chronic respiratory disease (CRD) in chickens, characterized by respiratory inflammation. S100A9 plays a pivotal role in modulating the inflammatory response to microbial pathogens. Our prior investigation revealed a significant upregulation of S100A9 in the lungs of chickens following MG infection. This study delves into the immunomodulatory effects of S100A9 during MG infection, demonstrating a notable increase in S100A9 levels in the lungs, immune organs, alveolar epithelial type II cells (AECII), and macrophage HD11 cells of MG-infected chicks and embryos. In MG-infected AECII cells, S100A9 overexpression significantly enhanced MG proliferation and adhesion, suppressed AVBD1, NFκB, pro-inflammatory factors (IL1ß and TNFα), and chemokines, reduced apoptosis, and promoted cell proliferation, thereby facilitating MG infection. Conversely, inhibiting S100A9 produced opposing effects. In MG-infected HD11 cells, S100A9 impeded MG proliferation and adhesion, increased AVBD1, NFκB, pro-inflammatory factors, and chemokines, and induced cell apoptosis while inhibiting proliferation. Additional results demonstrated that S100A9 facilitates MG infection by modulating the TLR7/NFκB/JAK/STAT pathway in AECII/HD11 cells. In summary, S100A9 exhibits a dual role in activating/inhibiting the natural immune response through TLR7/NFκB/JAK/STAT pathway regulation. This dual role promotes MG infection in AECII cells while enabling MG to evade immune surveillance by HD11 cells, ultimately enhancing the overall infection process. These findings advance our understanding of host-pathogen interactions during MG infection and underscore S100A9's potential as a therapeutic target for CRD in chickens.


Assuntos
Calgranulina B , Galinhas , Infecções por Mycoplasma , Mycoplasma gallisepticum , Doenças das Aves Domésticas , Animais , Mycoplasma gallisepticum/imunologia , Infecções por Mycoplasma/veterinária , Infecções por Mycoplasma/imunologia , Infecções por Mycoplasma/microbiologia , Galinhas/imunologia , Doenças das Aves Domésticas/microbiologia , Doenças das Aves Domésticas/imunologia , Calgranulina B/genética , Calgranulina B/metabolismo , Linhagem Celular , Pulmão/microbiologia , Pulmão/imunologia , Embrião de Galinha , NF-kappa B/metabolismo , Proliferação de Células , Macrófagos/imunologia , Macrófagos/microbiologia
19.
J Biophotonics ; 17(9): e202400168, 2024 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-38962821

RESUMO

Fundus photography (FP) is a crucial technique for diagnosing the progression of ocular and systemic diseases in clinical studies, with wide applications in early clinical screening and diagnosis. However, due to the nonuniform illumination and imbalanced intensity caused by various reasons, the quality of fundus images is often severely weakened, brings challenges for automated screening, analysis, and diagnosis of diseases. To resolve this problem, we developed strongly constrained generative adversarial networks (SCGAN). The results demonstrate that the quality of various datasets were more significantly enhanced based on SCGAN, simultaneously more effectively retaining tissue and vascular information under various experimental conditions. Furthermore, the clinical effectiveness and robustness of this model were validated by showing its improved ability in vascular segmentation as well as disease diagnosis. Our study provides a new comprehensive approach for FP and also possesses the potential capacity to advance artificial intelligence-assisted ophthalmic examination.


Assuntos
Fundo de Olho , Processamento de Imagem Assistida por Computador , Humanos , Processamento de Imagem Assistida por Computador/métodos , Aumento da Imagem/métodos , Redes Neurais de Computação
20.
Anticancer Drugs ; 35(8): 780-788, 2024 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-38958648

RESUMO

The aim of this study was to observe the therapeutic effect of sintilimab combined with a modified docetaxel + cisplatin + fluorouracil (DCF) regimen on advanced gastric cancer and its effect on Th1/Th2 immune balance. Ninety-eight cases of advanced gastric cancer patients who visited our hospital from April 2020 to May 2022 were selected and divided into 48 cases each in the conventional group and the research group by random number table method; the DCF regimen was adopted in the conventional group, and sintilimab combined with modified DCF regimen was adopted in the research group, and the therapeutic effects of the patients in the two groups and the changes of Th1/Th2 immune indexes were compared. CEA, CA199, CA242, CD168 AQ3, and IL-4 in the study group were lower than those in the conventional group at the end of three cycles of treatment, and the difference was statistically significant ( P  < 0.001). The levels of IFN-γ and IL-4 in the study group at the end of three cycles of treatment were higher than those in the conventional group ( P  < 0.001). The incidence of adverse reactions during treatment in the study group was lower than that in the conventional group ( P  < 0.001), and the grading of adverse reactions in the study group was milder than that in the conventional group. Sintilimab combined with a modified DCF regimen in the treatment of advanced gastric cancer not only improves the therapeutic effect but also positively affects the Th1/Th2 immune balance, which provides better immune regulation for patients with advanced gastric cancer.


Assuntos
Anticorpos Monoclonais Humanizados , Protocolos de Quimioterapia Combinada Antineoplásica , Cisplatino , Docetaxel , Fluoruracila , Neoplasias Gástricas , Humanos , Neoplasias Gástricas/tratamento farmacológico , Neoplasias Gástricas/imunologia , Neoplasias Gástricas/patologia , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Masculino , Feminino , Pessoa de Meia-Idade , Anticorpos Monoclonais Humanizados/administração & dosagem , Anticorpos Monoclonais Humanizados/uso terapêutico , Anticorpos Monoclonais Humanizados/efeitos adversos , Fluoruracila/administração & dosagem , Cisplatino/administração & dosagem , Docetaxel/administração & dosagem , Docetaxel/uso terapêutico , Interleucina-4 , Equilíbrio Th1-Th2/efeitos dos fármacos , Idoso , Células Th1/imunologia , Células Th1/efeitos dos fármacos , Interferon gama , Células Th2/imunologia , Células Th2/efeitos dos fármacos , Adulto
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