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1.
Heliyon ; 10(15): e34974, 2024 Aug 15.
Artículo en Inglés | MEDLINE | ID: mdl-39145011

RESUMEN

Purpose: Pathological fibrosis of the myodural bridge (MDB) affects cerebrospinal fluid circulation. However, no optimal drug treatments are available. We aimed to explore the antifibrotic effect of resveratrol on bleomycin-induced pathological fibrosis of the MDB and its underlying mechanisms. Methods: Genes common to the potential targets of resveratrol were determined using network pharmacology, genes related to muscle and tendon fibrosis were acquired from the GeneCards database, and genes related to MDB development were determined using Venny. These genes were considered potential resveratrol treatment targets in bleomycin-induced pathological fibrosis of the MDB and were annotated using bioinformatics methods. We validated the intersected genes using quantitative real-time polymerase chain reaction (qRT-PCR) and performed molecular docking analysis to calculate the binding activity between the target gene and resveratrol. Hematoxylin and eosin and Masson staining were used to detect the morphological changes in bleomycin-induced fibrosis of the MDB following resveratrol treatment. We used qRT-PCR and immunohistochemistry to evaluate the expression of the sirtuin 3 (SIRT3)/transforming growth factor-ß1 (TGF-ß1)/Smad pathway and the profibrotic markers α-smooth muscle actin (α-SMA) and Collagen Ⅰ. Results: Through network pharmacology and bioinformatics analyses, we identified four core intersected genes, and SIRT3 expression was validated using qRT-PCR. Molecular docking analysis revealed that resveratrol had good binding affinity for SIRT3. Resveratrol ameliorated morphological abnormalities in bleomycin-induced pathological fibrosis of the MDB by inhibiting fibroblast activation and excessive collagen fiber deposition. Resveratrol exerted its antifibrotic effect by regulating the SIRT3/TGF-ß1/Smad pathway. Conclusion: Resveratrol has an antifibrotic effect in bleomycin-induced pathological fibrosis of the MDB in vivo and may be considered a novel therapeutic strategy.

2.
Int J Biol Macromol ; : 134815, 2024 Aug 16.
Artículo en Inglés | MEDLINE | ID: mdl-39154690

RESUMEN

Oxidative stress plays an important role in various diseases. miR-221 has been reported to regulate oxidative stress. However, the mechanism of miR-221 in regulating oxidative stress induced by sCPPS5 remains unclear. This study aimed to investigate the protective effects and mechanisms of miR-221 on oxidative stress induced by sCPPS5. The expression of SOD, CAT, MDA, LDH, MMP, caspase-3 activity and apoptosis were measured. In addition, the key signaling factors in the Keap1-Nrf2-ARE signaling pathway were determined by real-time PCR and Western blot. Mice were employed to evaluate the effects of sCPPS5 and the possible mechanism in vivo. sCPPS5 promoted the expression of SOD and CAT and activated Keap1-Nrf2-ARE signaling pathway inhibit the MDA content, MMP, caspase-3 activity, apoptosis and LDH release rate after transfection with miR-221 mimics and inhibitors. Consistently, sCPPS5 has the potential to enhance the expression of antioxidant enzymes as well as upregulate mRNA expression of crucial signal proteins in vivo. miR-221 on oxidative stress protection induced by sCPPS5 possibly through regulating the Keap1-Nrf2-ARE signaling pathway in macrophages.

3.
BMC Biotechnol ; 24(1): 55, 2024 Aug 12.
Artículo en Inglés | MEDLINE | ID: mdl-39135175

RESUMEN

BACKGROUND: Diffuse large B-cell lymphoma (DLBCL) is a malignant tumour. Although some standard therapies have been established to improve the cure rate, they remain ineffective for specific individuals. Therefore, it is meaningful to find more novel therapeutic approaches. Macrophage polarisation is extensively involved in the process of tumour development. Recombinant hirudin (rH) affects macrophages and has been researched frequently in clinical trials lately. Our article validated the regulatory role of rH in macrophage polarisation and the mechanism of PAR-1 by collecting clinical samples and subsequently establishing a cellular model to provide a scientifically supported perspective for discovering new therapeutic approaches. METHOD: We assessed the expression of macrophage polarisation markers, cytokines and PAR-1 in clinical samples. We established a cell model by co-culture with THP-1 and OCI-Ly10 cell. We determined the degree of cell polarisation and expression of validation cytokines by flow cytometry, ELISA, and RT-qPCR to confirm the success of the cell model. Subsequently, different doses of rH were added to discover the function of rH on cell polarisation. We confirmed the mechanism of PAR-1 in macrophage polarisation by transfecting si-PAR-1 and pcDNA3.1-PAR-1. RESULTS: We found higher expression of M2 macrophage markers (CD163 + CMAF+) and PAR-1 in 32 DLBCL samples. After inducing monocyte differentiation into M0 macrophages and co-culturing with OCI-Ly10 lymphoma cells, we found a trend of these expressions in the cell model consistent with the clinical samples. Subsequently, we discovered that rH promotes the polarisation of M1 macrophages but inhibits the polarisation of M2 macrophages. We also found that PAR-1 regulates macrophage polarisation, inhibiting cell proliferation, migration, invasion and angiogenic capacity. CONCLUSION: rH inhibits macrophage polarisation towards the M2 type and PAR-1 regulates polarisation, proliferation, migration, invasion, and angiogenesis of DLBCL-associated macrophages.


Asunto(s)
Hirudinas , Linfoma de Células B Grandes Difuso , Macrófagos , Receptor PAR-1 , Proteínas Recombinantes , Linfoma de Células B Grandes Difuso/metabolismo , Linfoma de Células B Grandes Difuso/genética , Humanos , Macrófagos/metabolismo , Macrófagos/efectos de los fármacos , Receptor PAR-1/metabolismo , Receptor PAR-1/genética , Hirudinas/farmacología , Proteínas Recombinantes/farmacología , Proteínas Recombinantes/genética , Proteínas Recombinantes/metabolismo , Línea Celular Tumoral , Técnicas de Cocultivo , Polaridad Celular/efectos de los fármacos , Femenino , Masculino , Citocinas/metabolismo , Persona de Mediana Edad , Células THP-1 , Anciano
4.
Evol Lett ; 8(4): 494-504, 2024 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-39100238

RESUMEN

Reindeer have long been served as vital subsistence resources for inhabitants of Arctic and subarctic regions owing to their domestication. However, the evolutionary relationships and divergence times among different reindeer populations, genetic traits that distinguish domesticated reindeer, and factors that contribute to their relative docility compared with that of other Cervidae specie, remain unclear. In this study, we sequenced the genomes of 32 individuals from wild and domestic reindeer populations that inhabit Arctic and subarctic regions. We found that reindeer experienced 2 or more independent domestication events characterized by weak artificial selection pressure and limited significant differences in genomic parameters between wild and domestic populations. Alterations in conserved noncoding elements in the reindeer genomes, particularly those associated with nervous system development, may have contributed to their domestication by rendering the nervous system less responsive. Together, our results suggest that inherent species-specific traits, rather than intense artificial selection, may have played a significant role in the relatively docile behavior of reindeer and offer valuable insights into the domestication process of these animals.

5.
ChemSusChem ; : e202401108, 2024 Jul 18.
Artículo en Inglés | MEDLINE | ID: mdl-39022814

RESUMEN

The development of advanced electrocatalysts for the abiotic direct glucose fuel cells (ADGFCs) is critical in the implantable devices in living organisms. The ligand effect in the Pt shell-alloy core nanocatalysts is known to influence the electrocatalytic reaction in interfacial structure. Herein, we reported the synthesis of ternary Pt@PdRu nanoalloy aerogels with ligand effect of PdRu on Pt-enriched surface through electrochemical cycling. Pt@PdRu aerogels with optimized Pt surface electronic structure exhibited high mass activity and specific activity of Pt@PdRu about 450 mA·mgPt-1 and 1.09 mA·cm-2, which were 1.4 and 1.6 times than that of commercial Pt/C. Meanwhile, Pt@PdRu aerogels have higher electrochemical stability comparable to commercial Pt/C. In-situ FTIR spectra results proved that the glucose oxidation reaction on Pt@PdRu aerogels followed the CO-free direct pathway reaction mechanism and part of the products are CO2 by completed oxidation. Furthermore, the ADGFC with Pt@PdRu ultrathin anode catalyst layer showed a much higher power density of 6.2 mW·cm-2 than commercial Pt/C (3.8 mW·cm-2). To simulate the blood fuel cell, the Pt@PdRu integrated membrane electrode assembly was exposed to glucose solution and a steady-state open circuit of approximately 0.6 V was achieved by optimizing the glucose concentration in cell system.

6.
Exp Ther Med ; 28(3): 352, 2024 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-39071899

RESUMEN

Hepatocellular carcinoma (HCC) is one of the most aggressive types of cancer. Although it has a high mortality rate, there is currently no effective treatment for HCC. Lenvatinib has traditionally been used as the first-line treatment for advanced HCC (aHCC); however, resistance to this therapy is common. It can be difficult to select effective second-line drugs to overcome lenvatinib resistance when treating aHCC. For patients with aHCC, poor treatment efficacy can result in patients missing the optimal treatment window and can lead to an irreversible situation. Lenalidomide has begun to be used to treat HCC; however, to the best of our knowledge, its efficacy in patients with lenvatinib-resistant HCC remains to be reported on in the literature. The present case report, to the best of our knowledge, describes the first case in the literature of a patient with lenvatinib-resistant aHCC who achieved a partial response after the treatment regimen was switched to lenalidomide. The present case report provides a promising novel route for the treatment of lenvatinib-resistant HCC.

7.
Poult Sci ; 103(9): 103988, 2024 Jun 18.
Artículo en Inglés | MEDLINE | ID: mdl-38970848

RESUMEN

Inactivated vaccines play an important role in preventing and controlling the epidemic caused by the H5 subtype avian influenza virus. The vaccine strains are updated in response to alterations in surface protein antigens, while an avian-derived vaccine internal backbone with a high replicative capacity in chicken embryonated eggs and MDCK cells is essential for vaccine development. In this study, we constructed recombinant viruses using the clade 2.3.4.4d A/chicken/Jiangsu/GY5/2017(H5N6, CkG) strain as the surface protein donor and the clade 2.3.4.4b A/duck/Jiangsu/84512/2017(H5N6, Dk8) strain with high replicative ability as an internal donor. After optimization, the integration of the M gene from the CkG into the internal genes from Dk8 (8GM) was selected as the high-yield vaccine internal backbone, as the combination improved the hemagglutinin1/nucleoprotein (HA1/NP) ratio in recombinant viruses. The r8GMΔG with attenuated hemagglutinin and neuraminidase from the CkG exhibited high-growth capacity in both chicken embryos and MDCK cell cultures. The inactivated r8GMΔG vaccine candidate also induced a higher hemagglutination inhibition antibody titer and microneutralization titer than the vaccine strain using PR8 as the internal backbone. Further, the inactivated r8GMΔG vaccine candidate provided complete protection against wild-type strain challenge. Therefore, our study provides a high-yield, easy-to-cultivate candidate donor as an internal gene backbone for vaccine development.

8.
J Nanobiotechnology ; 22(1): 321, 2024 Jun 08.
Artículo en Inglés | MEDLINE | ID: mdl-38849841

RESUMEN

Acute lung injury (ALI) is a life threatening disease in critically ill patients, and characterized by excessive reactive oxygen species (ROS) and inflammatory factors levels in the lung. Multiple evidences suggest that nanozyme with diversified catalytic capabilities plays a vital role in this fatal lung injury. At present, we developed a novel class of polydopamine (PDA) coated cerium dioxide (CeO2) nanozyme (Ce@P) that acts as the potent ROS scavenger for scavenging intracellular ROS and suppressing inflammatory responses against ALI. Herein, we aimed to identify that Ce@P combining with NIR irradiation could further strengthen its ROS scavenging capacity. Specifically, NIR triggered Ce@P exhibited the most potent antioxidant and anti-inflammatory behaviors in lipopolysaccharide (LPS) induced macrophages through decreasing the intracellular ROS levels, down-regulating the levels of TNF-α, IL-1ß and IL-6, up-regulating the level of antioxidant cytokine (SOD-2), inducing M2 directional polarization (CD206 up-regulation), and increasing the expression level of HSP70. Besides, we performed intravenous (IV) injection of Ce@P in LPS induced ALI rat model, and found that it significantly accumulated in the lung tissue for 6 h after injection. It was also observed that Ce@P + NIR presented the superior behaviors of decreasing lung inflammation, alleviating diffuse alveolar damage, as well as promoting lung tissue repair. All in all, it has developed the strategy of using Ce@P combining with NIR irradiation for the synergistic enhanced treatment of ALI, which can serve as a promising therapeutic strategy for the clinical treatment of ROS derived diseases as well.


Asunto(s)
Lesión Pulmonar Aguda , Cerio , Indoles , Polímeros , Especies Reactivas de Oxígeno , Cerio/química , Cerio/farmacología , Animales , Lesión Pulmonar Aguda/tratamiento farmacológico , Polímeros/química , Polímeros/farmacología , Indoles/química , Indoles/farmacología , Especies Reactivas de Oxígeno/metabolismo , Ratas , Ratones , Masculino , Células RAW 264.7 , Pulmón/efectos de los fármacos , Pulmón/patología , Antioxidantes/farmacología , Antioxidantes/química , Ratas Sprague-Dawley , Lipopolisacáridos/farmacología , Antiinflamatorios/farmacología , Antiinflamatorios/química , Rayos Infrarrojos , Depuradores de Radicales Libres/farmacología , Depuradores de Radicales Libres/química , Depuradores de Radicales Libres/uso terapéutico , Nanopartículas/química , Macrófagos/efectos de los fármacos , Macrófagos/metabolismo , Citocinas/metabolismo
9.
Appl Opt ; 63(12): 3092-3098, 2024 Apr 20.
Artículo en Inglés | MEDLINE | ID: mdl-38856452

RESUMEN

A novel, to the best of our knowledge, photodetector with a metalens packaging module used as the visible light communication (VLC) receiver is proposed and designed. An LED consisting of red, green, blue, and yellow chips (RGBY-LED) is adopted as the transmitter for intensity modulation direct detection VLC systems. A metalens array with a numerical aperture (NA) of 0.707 used as a polarization-insensitive planar lens of the VLC system receiver is designed at wavelengths of 457, 523, 592, and 623 nm corresponding to blue, green, yellow, and red for high efficiency. Compared with a traditional Fresnel lens positive-intrinsic-negative (PIN) photodetector module as the VLC receiver, the introduction of a metalens module can decrease the form factor of the VLC receiver module and, in particular, it is much thinner. The combination of the multi-color LED transmitter and photodetector metalens packaging module receiver can increase the modulation bandwidth due to four different wavelengths used for the VLC system. Finite-difference time domain (FDTD) simulations are performed to validate the performance of the photodetector with a metalens module. It is revealed that the corresponding efficiencies of 57.5%, 55.4%, 57%, and 56.3% were achieved at wavelengths of 623, 592, 523, and 457 nm, respectively, based on a metalens array with a 0.707 NA and 2.5 µm radius of the active area of the photodetector. It is a promising technology for indoor VLC systems such as those for smart phones and other Internet of Things devices due to the need for compact packaging for the receiver.

10.
Sci Rep ; 14(1): 13891, 2024 Jun 17.
Artículo en Inglés | MEDLINE | ID: mdl-38880799

RESUMEN

Traditional DID models overlook variations in policy intensity, causing estimation deviations from the actual situation and a limited understanding of the influence mechanism. In response, the Intensity Modified SDID Model is built to examine the influence mechanism of ETS's carbon reductions. Moreover, through model extensions, the study explores the spatiotemporal characteristics and heterogeneities of ETS's effects. Results show that: (1) "Dual-circulation" influence mechanism is confirmed, where ETS directly contributes to carbon reductions (2.70% to 10.0% impact) through external pathways, and internal pathways continuously strengthen reduction effects, comprehensive mechanisms are thereby formed and enhanced based on interaction among internal and external pathways. (2) Reasonable ETS levels are estimated and proposed to achieve "Dual Carbon Target", constraining nationwide carbon quotas by 20 billion tons/year, increasing carbon trading volumes by 80 thousand tons/year, and elevating the carbon trading prices by 100 RMB (14 USD) per ton. (3) ETS's carbon reduction effects are identified with temporal and spatial characteristics, temporally, effects peak in the 4th period (Event+4) but diminish in the 5th period (Event+5), spatially, effects peak in areas distancing around 1000 km but disappear beyond 1500 km. (4) ETS also has synergistic effects with atmospheric pollution reduction, including industrial emissions of sulfur dioxide and smoke (dust), but are insignificant to industrial emissions of wastewater and solid waste.

11.
Methods Mol Biol ; 2832: 133-144, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38869792

RESUMEN

Plant long non-coding RNAs (lncRNAs) have been implicated in many biological processes, including responses to abiotic stresses, yet their detailed functions and especially their modes of action are still underexplored. lncRNAs often interact with proteins to participate in multiple levels of gene regulation. Therefore, identifying the RNA-binding proteins and validating their interaction with lncRNAs will be instrumental in revealing the functions of lncRNAs. Here, we describe two major methods to determine the interaction between lncRNA and proteins in vitro, RNA pull-down, and RNA EMSA.


Asunto(s)
ARN Largo no Codificante , Proteínas de Unión al ARN , ARN Largo no Codificante/genética , ARN Largo no Codificante/metabolismo , Proteínas de Unión al ARN/metabolismo , Proteínas de Unión al ARN/genética , Estrés Fisiológico/genética , Ensayo de Cambio de Movilidad Electroforética/métodos , ARN de Planta/genética , ARN de Planta/metabolismo , Unión Proteica
12.
PLoS One ; 19(5): e0289854, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38771750

RESUMEN

INTRODUCTION: Recent research suggests that endothelial activation plays a role in coronavirus disease 2019 (COVID-19) pathogenesis by promoting a pro-inflammatory state. However, the mechanism by which the endothelium is activated in COVID-19 remains unclear. OBJECTIVE: To investigate the mechanism by which COVID-19 activates the pulmonary endothelium and drives pro-inflammatory phenotypes. HYPOTHESIS: The "inflammatory load or burden" (cytokine storm) of the systemic circulation activates endothelial NADPH oxidase 2 (NOX2) which leads to the production of reactive oxygen species (ROS) by the pulmonary endothelium. Endothelial ROS subsequently activates pro-inflammatory pathways. METHODS: The inflammatory burden of COVID-19 on the endothelial network, was recreated in vitro, by exposing human pulmonary microvascular endothelial cells (HPMVEC) to media supplemented with serum from COVID-19 affected individuals (sera were acquired from patients with COVID-19 infection that eventually died. Sera was isolated from blood collected at admission to the Intensive Care Unit of the Hospital of the University of Pennsylvania). Endothelial activation, inflammation and cell death were assessed in HPMVEC treated with serum either from patients with COVID-19 or from healthy individuals. Activation was monitored by measuring NOX2 activation (Rac1 translocation) and ROS production; inflammation (or appearance of a pro-inflammatory phenotype) was monitored by measuring the induction of moieties such as intercellular adhesion molecule (ICAM-1), P-selectin and the NLRP3 inflammasome; cell death was measured via SYTOX™ Green assays. RESULTS: Endothelial activation (i.e., NOX2 activation and subsequent ROS production) and cell death were significantly higher in the COVID-19 model than in healthy samples. When HPMVEC were pre-treated with the novel peptide PIP-2, which blocks NOX2 activation (via inhibition of Ca2+-independent phospholipase A2, aiPLA2), significant abrogation of ROS was observed. Endothelial inflammation and cell death were also significantly blunted. CONCLUSIONS: The endothelium is activated during COVID-19 via cytokine storm-driven NOX2-ROS activation, which causes a pro-inflammatory phenotype. The concept of endothelial NOX2-ROS production as a unifying pathophysiological axis in COVID-19 raises the possibility of using PIP-2 to maintain vascular health.


Asunto(s)
COVID-19 , Células Endoteliales , NADPH Oxidasa 2 , Especies Reactivas de Oxígeno , SARS-CoV-2 , Transducción de Señal , Humanos , COVID-19/metabolismo , Especies Reactivas de Oxígeno/metabolismo , Células Endoteliales/metabolismo , SARS-CoV-2/fisiología , NADPH Oxidasa 2/metabolismo , Endotelio Vascular/metabolismo , Pulmón/patología , Pulmón/metabolismo , Pulmón/virología , Pulmón/irrigación sanguínea , Péptidos/metabolismo , Molécula 1 de Adhesión Intercelular/metabolismo
13.
PLoS One ; 19(5): e0303084, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38753685

RESUMEN

The advent of smart grid technologies has brought about a paradigm shift in the management and operation of distribution networks, allowing for intricate system information to be encapsulated within semantic network models. These models, while robust, are not immune to faults within their knowledge entities, which can arise from a myriad of issues, potentially leading to verification failures and operational disruptions. Addressing this critical vulnerability, our research delves into the development of a novel fault detection methodology specifically tailored for the knowledge entity variables of semantic networks in distribution networks. In our approach, we first construct a state space equation that models the behavior of knowledge entity variables in the presence of faults. This foundational framework enables us to apply an unknown input observer strategy to effectively detect anomalies within the system. To bolster the fault identification process, we introduce the innovative use of a siamese network, a neural network architecture which is proficient in differentiating between similar datasets. Through simulation scenarios, we demonstrate the efficacy of our proposed fault detection method.


Asunto(s)
Redes Neurales de la Computación , Semántica , Algoritmos , Simulación por Computador
14.
J Transl Med ; 22(1): 512, 2024 May 28.
Artículo en Inglés | MEDLINE | ID: mdl-38807223

RESUMEN

In cancer treatment, therapeutic strategies that integrate tumor-specific characteristics (i.e., precision oncology) are widely implemented to provide clinical benefits for cancer patients. Here, through in-depth integration of tumor transcriptome and patients' prognoses across cancers, we investigated dysregulated and prognosis-associated genes and catalogued such important genes in a cancer type-dependent manner. Utilizing the expression matrices of these genes, we built models to quantitatively evaluate the malignant levels of tumors across cancers, which could add value to the clinical staging system for improved prediction of patients' survival. Furthermore, we performed a transcriptome-based molecular subtyping on hepatocellular carcinoma, which revealed three subtypes with significantly diversified clinical outcomes, mutation landscapes, immune microenvironment, and dysregulated pathways. As tumor transcriptome was commonly profiled in clinical practice with low experimental complexity and cost, this work proposed easy-to-perform approaches for practical clinical promotion towards better healthcare and precision oncology of cancer patients.


Asunto(s)
Regulación Neoplásica de la Expresión Génica , Neoplasias , Medicina de Precisión , Transcriptoma , Humanos , Transcriptoma/genética , Neoplasias/genética , Neoplasias/clasificación , Neoplasias/patología , Pronóstico , Perfilación de la Expresión Génica , Carcinoma Hepatocelular/genética , Carcinoma Hepatocelular/clasificación , Carcinoma Hepatocelular/patología , Mutación/genética , Microambiente Tumoral/genética , Neoplasias Hepáticas/genética , Neoplasias Hepáticas/clasificación , Neoplasias Hepáticas/patología , Oncología Médica/métodos
15.
Eur J Med Res ; 29(1): 253, 2024 Apr 24.
Artículo en Inglés | MEDLINE | ID: mdl-38659000

RESUMEN

The progression of heart failure (HF) is complex and involves multiple regulatory pathways. Iron ions play a crucial supportive role as a cofactor for important proteins such as hemoglobin, myoglobin, oxidative respiratory chain, and DNA synthetase, in the myocardial energy metabolism process. In recent years, numerous studies have shown that HF is associated with iron dysmetabolism, and deficiencies in iron and overload of iron can both lead to the development of various myocarditis diseases, which ultimately progress to HF. Iron toxicity and iron metabolism may be key targets for the diagnosis, treatment, and prevention of HF. Some iron chelators (such as desferrioxamine), antioxidants (such as ascorbate), Fer-1, and molecules that regulate iron levels (such as lactoferrin) have been shown to be effective in treating HF and protecting the myocardium in multiple studies. Additionally, certain natural compounds can play a significant role by mediating the imbalance of iron-related signaling pathways and expression levels. Therefore, this review not only summarizes the basic processes of iron metabolism in the body and the mechanisms by which they play a role in HF, with the aim of providing new clues and considerations for the treatment of HF, but also summarizes recent studies on natural chemical components that involve ferroptosis and its role in HF pathology, as well as the mechanisms by which naturally occurring products regulate ferroptosis in HF, with the aim of providing reference information for the development of new ferroptosis inhibitors and lead compounds for the treatment of HF in the future.


Asunto(s)
Productos Biológicos , Insuficiencia Cardíaca , Hierro , Humanos , Insuficiencia Cardíaca/metabolismo , Insuficiencia Cardíaca/tratamiento farmacológico , Hierro/metabolismo , Productos Biológicos/uso terapéutico , Productos Biológicos/farmacología , Animales , Ferroptosis/efectos de los fármacos , Quelantes del Hierro/uso terapéutico , Quelantes del Hierro/farmacología , Antioxidantes/uso terapéutico
16.
Ann Vasc Surg ; 105: 227-235, 2024 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-38609009

RESUMEN

BACKGROUND: Studies have linked matrix metalloproteinases (MMPs) to both thoracic aortic aneurysm and abdominal aortic aneurysm (TAA and AAA). The precise MMPs entailed in this procedure, however, were still unknown. This study used a two-sample Mendelian randomization (MR) analysis to look into the causal relationship between MMPs and the risk of TAA and AAA. METHODS: Eight MMPs, including MMP-1, MMP-2, MMP-3, MMP-8, MMP-9, MMP-10, MMP-12, and MMP-13, were found among people of European ancestry with accessible Genome-Wide Association Studies (GWAS). We employed the findings from Genome-Wide Association Studies (GWAS) for 8 MMPs, and TAA and AAA from the FinnGen consortiums (3,201 cases and 317,899 controls, respectively) were used in a two-sample MR analysis. The primary method of analysis for MR was the inverse variance weighted (IVW) method, along with analyses of heterogeneity and horizontal pleiotropy. 31 single-nucleotide polymorphisms connected to MMP were retrieved. RESULTS: IVW demonstrated a negative causal association between TAA and AAA and serum MMP-12 levels. The incidence of TAA decreased by 1.031% for every 1 ng/mL increase in serum MMP-12 [odds ratio (OR) = 0.897, 95% confidence interval (CI): 0.831-0.968, P = 0.005]. The incidence of AAA fell by 1.653% (OR = 0.835, 95% CI: 0.752-0.926, P = 0.001) for every 1 ng/mL increase in serum MMP-12. There was no horizontal pleiotropy or heterogeneity in the MR data (P > 0.05). CONCLUSIONS: The levels of TAA and AAA and serum MMP-12 are causally related. MMP-12 is a factor that reduces the risk of AAA and TTA. Our study suggested that MMP-12 level is causally associated with a decreased risk of TAA and AAA.


Asunto(s)
Aneurisma de la Aorta Abdominal , Aneurisma de la Aorta Torácica , Metaloproteinasas de la Matriz , Humanos , Aneurisma de la Aorta Abdominal/genética , Aneurisma de la Aorta Abdominal/enzimología , Aneurisma de la Aorta Abdominal/diagnóstico por imagen , Aneurisma de la Aorta Abdominal/sangre , Aneurisma de la Aorta Abdominal/epidemiología , Aneurisma de la Aorta Torácica/genética , Aneurisma de la Aorta Torácica/enzimología , Aneurisma de la Aorta Torácica/sangre , Aneurisma de la Aorta Torácica/diagnóstico por imagen , Aneurisma de la Aorta Torácica/epidemiología , Estudios de Casos y Controles , Predisposición Genética a la Enfermedad , Estudio de Asociación del Genoma Completo , Incidencia , Metaloproteinasa 12 de la Matriz/genética , Metaloproteinasa 12 de la Matriz/sangre , Metaloproteinasas de la Matriz/genética , Metaloproteinasas de la Matriz/sangre , Análisis de la Aleatorización Mendeliana , Fenotipo , Polimorfismo de Nucleótido Simple , Factores Protectores , Medición de Riesgo , Factores de Riesgo
17.
Chem Biol Drug Des ; 103(5): e14533, 2024 May.
Artículo en Inglés | MEDLINE | ID: mdl-38684373

RESUMEN

Hirudin is one of the specific inhibitors of thrombin, which has been confirmed to have strong bioactivities, including inhibiting tumors. However, the function and mechanism of hirudin and protease-activated receptor 1 (PAR-1) in diffuse large B-cell lymphoma (DLBCL) have not been clear. Detecting the expression PAR-1 in DLBCL tissues and cells by RT-qPCR and IHC. Transfected sh-NC, sh-PAR-1, or pcDNA3.1-PAR-1 in DLBCL cells or processed DLBCL cells through added thrombin, Vorapaxar, Recombinant hirudin (RH), or Na2S2O4 and co-culture with EA.hy926. And built DLBCL mice observed tumor growth. Detecting the expression of related genes by RT-qPCR, Western blot, IHC, and immunofluorescence, measured the cellular hypoxia with Hypoxyprobe-1 Kit, and estimated the cell inflammatory factors, proliferation, migration, invasion, and apoptosis by ELISA, CCK-8, flow cytometry, wound-healing and Transwell. Co-immunoprecipitation and pull-down measurement were used to verify the relationship. PAR-1 was highly expressed in DLBCL tissues and cells, especially in SUDHL2. Na2S2O4 induced SUDHL2 hypoxia, and PAR-1 did not influence thrombin-activated hypoxia. PAR-1 could promote SUDHL2 proliferation, migration, and invasion, and it was unrelated to cellular hypoxia. PAR-1 promoted proliferation, migration, and angiogenesis of EA.hy926 or SUDHL2 through up-regulation vascular endothelial growth factor (VEGF). RH inhibited tumor growth, cell proliferation, and migration, promoted apoptosis of DLBCL, and inhibited angiogenesis by down-regulating PAR-1-VEGF. RH inhibits proliferation, migration, and angiogenesis of DLBCL cells by down-regulating PAR-1-VEGF.


Asunto(s)
Apoptosis , Proliferación Celular , Hirudinas , Linfoma de Células B Grandes Difuso , Neovascularización Patológica , Receptor PAR-1 , Proteínas Recombinantes , Factor A de Crecimiento Endotelial Vascular , Humanos , Hirudinas/farmacología , Receptor PAR-1/metabolismo , Receptor PAR-1/antagonistas & inhibidores , Linfoma de Células B Grandes Difuso/metabolismo , Linfoma de Células B Grandes Difuso/tratamiento farmacológico , Linfoma de Células B Grandes Difuso/patología , Animales , Factor A de Crecimiento Endotelial Vascular/metabolismo , Factor A de Crecimiento Endotelial Vascular/genética , Ratones , Línea Celular Tumoral , Neovascularización Patológica/tratamiento farmacológico , Neovascularización Patológica/metabolismo , Apoptosis/efectos de los fármacos , Proteínas Recombinantes/farmacología , Proteínas Recombinantes/metabolismo , Proliferación Celular/efectos de los fármacos , Movimiento Celular/efectos de los fármacos , Angiogénesis
18.
Parasit Vectors ; 17(1): 135, 2024 Mar 15.
Artículo en Inglés | MEDLINE | ID: mdl-38491403

RESUMEN

BACKGROUND: The geographic distribution and host-parasite interaction networks of Sarcocystis spp. in small mammals in eastern Asia remain incompletely known. METHODS: Experimental infections, morphological and molecular characterizations were used for discrimination of a new Sarcocystis species isolated from colubrid snakes and small mammals collected in Thailand, Borneo and China. RESULTS: We identified a new species, Sarcocystis muricoelognathis sp. nov., that features a relatively wide geographic distribution and infects both commensal and forest-inhabiting intermediate hosts. Sarcocystis sporocysts collected from rat snakes (Coelognathus radiatus, C. flavolineatus) in Thailand induced development of sarcocysts in experimental SD rats showing a type 10a cyst wall ultrastructure that was identical with those found in Rattus norvegicus from China and the forest rat Maxomys whiteheadi in Borneo. Its cystozoites had equal sizes in all intermediate hosts and locations, while sporocysts and cystozoites were distinct from other Sarcocystis species. Partial 28S rRNA sequences of S. muricoelognathis from M. whiteheadi were largely identical to those from R. norvegicus in China but distinct from newly sequenced Sarcocystis zuoi. The phylogeny of the nuclear 18S rRNA gene placed S. muricoelognathis within the so-called S. zuoi complex, including Sarcocystis attenuati, S. kani, S. scandentiborneensis and S. zuoi, while the latter clustered with the new species. However, the phylogeny of the ITS1-region confirmed the distinction between S. muricoelognathis and S. zuoi. Moreover, all three gene trees suggested that an isolate previously addressed as S. zuoi from Thailand (KU341120) is conspecific with S. muricoelognathis. Partial mitochondrial cox1 sequences of S. muricoelognathis were almost identical with those from other members of the group suggesting a shared, recent ancestry. Additionally, we isolated two partial 28S rRNA Sarcocystis sequences from Low's squirrel Sundasciurus lowii that clustered with those of S. scandentiborneensis from treeshews. CONCLUSIONS: Our results provide strong evidence of broad geographic distributions of rodent-associated Sarcocystis and host shifts between commensal and forest small mammal species, even if the known host associations remain likely only snapshots of the true associations.


Asunto(s)
Enfermedades de los Roedores , Sarcocystis , Sarcocistosis , Ratas , Animales , Sarcocistosis/veterinaria , Sarcocistosis/parasitología , ARN Ribosómico 28S/genética , Reacción en Cadena de la Polimerasa , Ratas Sprague-Dawley , ARN Ribosómico 18S/genética , Filogenia , Sciuridae , Murinae , Enfermedades de los Roedores/parasitología
19.
Vaccine ; 42(10): 2608-2620, 2024 Apr 11.
Artículo en Inglés | MEDLINE | ID: mdl-38472066

RESUMEN

The present Porcine circovirus type 2 virus (PCV2) vaccine adjuvants suffer from numerous limitations, such as adverse effects, deficient cell-mediated immune responses, and inadequate antibody production. In this study, we explored the potential of a novel nanoparticle (CS-Au NPs) based on gold nanoparticles (Au NPs) and chitosan (CS) that modified Viola philippica polysaccharide (VPP) as efficient adjuvants for PCV2 vaccine. The characterization demonstrated that CS-Au-VPP NPs had a mean particle size of 507.42 nm and a zeta potential value of -21.93 mV. CS-Au-VPP NPs also exhibited good dispersion and a stable structure, which did not alter the polysaccharide properties. Additionally, the CS-Au-VPP NPs showed easy absorption and utilization by the organism. To investigate their immune-enhancing potential, mice were immunized with a mixture of CS-Au-VPP NPs and PCV2 vaccine. The evaluation of relevant immunological indicators, including specific IgG antibodies and their subclasses, cytokines, and T cell subpopulations, confirmed their immune-boosting effects. The in vivo experiments revealed that the medium-dose CS-Au-VPP NPs significantly elevated the levels of specific IgG antibodies and their subclasses, cytokines, and T cell subpopulations in PCV2-immunized mice. These findings suggest that CS-Au-VPP NPs can serve as a promising vaccine adjuvant due to their stable structure and immunoenhancement capabilities.


Asunto(s)
Quitosano , Nanopartículas del Metal , Nanopartículas , Vacunas , Viola , Porcinos , Animales , Ratones , Oro/química , Quitosano/química , Nanopartículas/química , Polisacáridos , Citocinas , Inmunoglobulina G
20.
Medicine (Baltimore) ; 103(11): e37329, 2024 Mar 15.
Artículo en Inglés | MEDLINE | ID: mdl-38489702

RESUMEN

To evaluate the impact of CO2 fractional laser combined with recombinant human epidermal growth factor (rhEGF) gel on skin barrier in acne scar patients. In a retrospective analysis, we examined 105 acne scar patients admitted between July 2018 and August 2021. Of these, 51 received only CO2 fractional laser (control group), while 54 underwent a combination of CO2 fractional laser and rhEGF gel (observation group). We assessed treatment efficacy, symptom relief, skin barrier parameters, pre- and posttreatment inflammatory factors, adverse reactions, posttreatment quality of life, and patient satisfaction. The observation group exhibited a higher overall response rate, significantly shorter wound healing, scab formation, and scab detachment times. Additionally, this group showed increased stratum corneum water content, decreased pH, and transdermal water loss (TEWL), and reduced hypersensitive C-reactive protein and interleukin-6 expression posttreatment. Quality of life scores were higher, with fewer adverse reactions and greater treatment satisfaction. Combining CO2 fractional laser with rhEGF gel markedly improves acne scar treatment efficacy, enhances skin barrier function, reduces inflammation, and elevates quality of life. Its safety profile supports its broader clinical adoption.


Asunto(s)
Acné Vulgar , Láseres de Gas , Humanos , Cicatriz/etiología , Cicatriz/terapia , Dióxido de Carbono , Acné Vulgar/terapia , Estudios Retrospectivos , Calidad de Vida , Resultado del Tratamiento , Factor de Crecimiento Epidérmico/uso terapéutico , Agua , Rayos Láser , Láseres de Gas/uso terapéutico
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