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1.
Life (Basel) ; 14(9)2024 Aug 23.
Artículo en Inglés | MEDLINE | ID: mdl-39337840

RESUMEN

Systemic sclerosis (SSc) is characterized by a complex interplay of vascular damage, inflammation, and fibrosis, affecting the skin and internal organs. Plasminogen activator inhibitor-1 (PAI-1), a protein encoded by the SERPINE1 gene, is a potential biomarker of SSc because it is primarily involved in fibrinolysis and is associated with the severity of some autoimmune diseases. This study aimed to determine the association between SERPINE1 variant -675 4G/5G and soluble PAI-1 (sPAI-1) levels with the clinical characteristics and risk of SSc in a Mexican population. This cross-sectional study included 56 SSc patients and 114 control subjects (CSs). The variant was genotyped via the PCR-RFLP method and the levels of sPAI-1 were determined using enzyme-linked immunosorbent assays (ELISAs). The -675 4G/5G variant was not associated with SSc risk or sPAI-I levels. However, higher sPAI-1 levels were observed in SSc patients than in CSs (p = 0.045); these levels were significantly correlated with age, platelets, glucose, and serum levels of transforming growth factor (TGF)-ß1, 2, and 3. The SERPINE1 -675 4G/5G variant did not show any association with SSc risk or sPAI-I levels. However, our study shows a possible alteration of sPAI-1 in this disease, which could be associated with the fibrotic and thrombotic processes in SSc.

2.
Sensors (Basel) ; 24(17)2024 Aug 26.
Artículo en Inglés | MEDLINE | ID: mdl-39275434

RESUMEN

With the expansion of wireless mobile networks into both the daily lives of individuals as well as into the widely developing market of connected devices, communication is an increasingly attractive target for attackers. As the complexity of mobile cellular systems grows and the respective countermeasures are implemented to secure data transmissions, the attacks have become increasingly sophisticated on the one hand, but at the same time the system complexity can open up expanded opportunities for security and privacy breaches. After an in-depth summary of possible entry points to attacks to mobile networks, this paper first briefly reviews the basic principles of the physical layer implementation of 4G/5G systems, then gives an overview of possible attacks from a physical layer perspective. It also provides an overview of the software frameworks and hardware tool-software defined radios currently in use for experimenting with 4G/5G mobile networks, and it discusses their basic capabilities. In the final part, the paper summarizes the currently most promising families of techniques to detect illegitimate base stations-the machine-learning-based, localization-based, and behavior-based methods.

3.
Cell Rep Med ; : 101731, 2024 Sep 14.
Artículo en Inglés | MEDLINE | ID: mdl-39303711

RESUMEN

Current therapies against pancreatic ductal adenocarcinoma (PDAC) have limited clinical benefits owing to tumor heterogeneity and their unique immunosuppressive microenvironments. The eukaryotic initiation factor (eIF) 4F complex is involved in regulating translation and various downstream carcinogenic signaling pathways. We report that eIF4G1, one of the subunits of eIF4F, is overexpressed in cancer cells and cancer-associated fibroblasts, and this correlates with poor prognosis in patients with PDAC. In PDAC mice, eIF4G1 inhibition limits tumor progression and prolongs overall survival, especially when combined with PD1/PDL1 antagonists and gemcitabine. Mechanistically, eIF4G1 inhibition hinders the production of cytokines and chemokines that promote fibrosis and inhibit cytotoxic T cell chemotaxis. Moreover, eIF4G1 inhibition impairs integrinß1 protein translation and exerts tumor suppression effects through the FAK-ERK/AKT signaling pathway. These findings highlight the effects of eIF4G1 on tumor immune dependence and independence and identify eIF4G1 as a promising therapeutic target for PDAC.

4.
Front Immunol ; 15: 1445294, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-39281671

RESUMEN

Introduction: Plasminogen activator inhibitor-1 (PAI-1) is linked to thrombosis and endothelial dysfunction in severe COVID-19. The +43 G>A PAI-1 and 4G/5G promoter polymorphism can influence PAI-1 expression. The 4G5G PAI-1 promoter gene polymorphism constitutes the 4G4G, 4G5G, and 5G5G genotypes. However, the impact of PAI-1 polymorphisms on disease severity or endothelial dysfunction remains unclear. Methods: Clinical data, sera, and peripheral blood mononuclear cells (PBMCs) of COVID-19 patients were studied. Results: Comorbidities and clinical biomarkers did not correlate with genotypes in either polymorphism. However, differences between fibrinolytic factors and interleukin-1ß (IL-1ß) were identified in genotypes of the 4G/5G but not the 43 G>A PAI polymorphism. Patients with the 4G4G genotype of the 4G/5G polymorphism showed high circulating PAI-1, mainly complexed with plasminogen activators, and low IL-1ß and plasmin levels, indicating suppressed fibrinolysis. NFκB was upregulated in PBMCs of COVID-19 patients with the 4G4G genotype. Discussion: Mechanistically, IL-1ß enhanced PAI-1 expression in 4G4G endothelial cells, preventing the generation of plasmin and cleavage products like angiostatin, soluble uPAR, and VCAM1. We identified inflammation-induced endothelial dysfunction coupled with fibrinolytic system overactivation as a risk factor for patients with the 5G5G genotype.


Asunto(s)
COVID-19 , Inhibidor 1 de Activador Plasminogénico , Regiones Promotoras Genéticas , SARS-CoV-2 , Humanos , Inhibidor 1 de Activador Plasminogénico/genética , COVID-19/genética , COVID-19/sangre , Masculino , Regiones Promotoras Genéticas/genética , Femenino , Persona de Mediana Edad , SARS-CoV-2/fisiología , Anciano , Índice de Severidad de la Enfermedad , Leucocitos Mononucleares/metabolismo , Polimorfismo de Nucleótido Simple , Interleucina-1beta/genética , Genotipo , Adulto
5.
Sci Rep ; 14(1): 21488, 2024 09 14.
Artículo en Inglés | MEDLINE | ID: mdl-39277597

RESUMEN

Graphite carbon nitride (g-C3N4) is a two-dimensional nano-sheet with electronic properties, which shows unique characteristics with high chemical and thermal stability in its structure. The functionalization of these compounds through covalent bonding is an important step towards significantly improving their properties and capabilities. To achieve this goal, a novel strategy for the covalent functionalization of Fe3O4@g-C3N4 with thiamine hydrochloride (vitamin B1) via cyanuric chloride (TCT), which is a divalent covalent linker, was presented. The efficiency of Fe3O4@gC3N4@Thiamine as a heterogeneous organic catalyst in the synthesis of spirooxindole-pyran derivatives and 2-amino-4H-pyran under solvent-free conditions was evaluated and the yields of high-purity products were presented. In addition, easy recycling and reuse for seven consecutive cycles without significant reduction in catalytic activity are other features of this catalyst. Moreover, the performance of the prepared sorbent in the microextraction technique (herein, magnetic solid phase extraction) was studied. The tebuconazole was selected as the target analyte. The target analyte was extracted and determined by HPLC-UV. Under the optimum condition, the linear range of the method (LDR) was estimated in the range of 0.2-100 µg L-1 (the coefficient of determination of 0.9962 for tebuconazole). The detection limit (LOD) of the method for tebuconazole was calculated to be 0.05 µg L-1. The limit of quantification (LOQ) of the method was also estimated to be 0.16 µg L-1. In order to check the precision of the proposed method, the intra-day and inter-day relative standard deviations (RSD%) were calculated, which were in the range of 1.5- 2.8%. The method was used for the successful extraction and determination of tebuconazole in tomato, cucumber, and carrot samples.


Asunto(s)
Grafito , Tiamina , Triazoles , Catálisis , Triazoles/química , Triazoles/análisis , Grafito/química , Tiamina/química , Tiamina/análisis , Contaminación de Alimentos/análisis , Análisis de los Alimentos/métodos , Compuestos Heterocíclicos/química , Compuestos Heterocíclicos/síntesis química , Compuestos de Nitrógeno/química , Microextracción en Fase Sólida/métodos , Compuestos Inorgánicos de Carbono/química
6.
J Proteome Res ; 2024 Aug 30.
Artículo en Inglés | MEDLINE | ID: mdl-39213495

RESUMEN

Hepatocellular carcinoma (HCC) is a highly lethal cancer, and proteomic studies have shown increased protein diversity and abundance in HCC tissues, whereas the role of protein translation has not been extensively explored in HCC. Our research focused on key molecules in the translation process to identify a potential contributor in HCC. We discovered that EIF4G2, a crucial translation initiation factor, is significantly upregulated in HCC tissues and associated with poor prognosis. This study uniquely highlights the impact of EIF4G2 deletion, which suppresses tumor growth and metastasis both in vitro and in vivo. Furthermore, polysome analysis and nascent protein synthesis assays revealed EIF4G2's role in regulating protein translation, specifically identifying PLEKHA1 as a key translational product. This represents a novel mechanistic insight into HCC malignancy. RNA immunoprecipitation (RIP) and Dual-luciferase reporter assays further revealed that EIF4G2 facilitates PLEKHA1 translation via an IRES-dependent manner. Importantly, the synergistic effects of EIF4G2 depletion and PLEKHA1 reduction in inhibiting cell migration and invasion underscore the therapeutic potential of targeting this axis. This study not only advances our understanding of translational regulation in HCC but also identifies the EIF4G2-PLEKHA1 axis as a promising therapeutic target, offering new avenues for intervention in HCC treatment.

7.
Molecules ; 29(16)2024 Aug 09.
Artículo en Inglés | MEDLINE | ID: mdl-39202852

RESUMEN

Ag3PO4/g-C3N4 photocatalytic composites were synthesized via calcination and hydrothermal synthesis for the degradation of rhodamine B (RhB) in wastewater, and characterized using X-ray diffraction (XRD), scanning electron microscopy (SEM), transmission electron microscopy (TEM), X-ray photoelectron spectroscopy (XPS), and diffuse reflectance spectroscopy (DRS). The degradation of RhB by Ag3PO4/g-C3N4 composites was investigated to evaluate their photocatalytic performance and cyclic degradation stability. The experimental results showed that the composites demonstrated notable photocatalytic activity and stability during degradation. Their high degradation efficiency is attributed to the Z-scheme transfer mechanism, in which the electrons in the Ag3PO4 conduction band and the holes in the g-C3N4 valence band are annihilated by heterojunction recombination, which greatly limits the recombination of photogenerated electrons and holes in the catalyst and enhances the activity of the composite photocatalyst. In addition, measurements of photocurrent (PC) and electrochemical impedance spectroscopy (EIS) confirmed that the efficient charge separation of photo-generated charges stemmed from strong interactions at the close contact interface. Finally, the mechanism for catalytic enhancement in the composite photocatalysts was proposed based on hole and radical trapping experiments, electron paramagnetic resonance (EPR) analysis, and work function evaluation.

8.
Vaccines (Basel) ; 12(8)2024 Jul 23.
Artículo en Inglés | MEDLINE | ID: mdl-39203958

RESUMEN

The transplacental transmission of CSFV and the resulting persistent congenital infection in newborn piglets have been abundantly discussed in pregnant sows suffering from virus infection. Importantly, the availability of safe commercial vaccines with proven efficacy to prevent the generation of congenital and postnatal persistent infections in pregnant sows are critical tools for controlling the disease in CSF endemic areas. Here, we demonstrate the high efficacy of a single dose of the recombinant FlagT4G vaccine to provide solid protection in pregnant sows against transplacental transmission of a highly virulent CSFV. Pregnant sows vaccinated with FlagT4G at 44 days of gestation elicited a strong CSFV-specific antibody response, with neutralizing antibody levels above those required for protection against CSFV. Importantly, after the challenge with a highly virulent CSFV, all foetuses from FlagT4G-vaccinated sows lacked CSF macroscopic lesions and showed a complete absence of the challenge virus in their internal organs at day 79 of gestation. Therefore, pregnant sows safely vaccinated with FlagT4G without affecting reproductive efficacy are efficaciously protected, along with their foetuses, against the infection and disease caused by a CSFV virulent field strain.

9.
Front Biosci (Landmark Ed) ; 29(7): 264, 2024 Jul 23.
Artículo en Inglés | MEDLINE | ID: mdl-39082355

RESUMEN

BACKGROUND: The ability to maintain muscle function decreases with age and loss of proteostatic function. Diet, drugs, and genetic interventions that restrict nutrients or nutrient signaling help preserve long-term muscle function and slow age-related decline. Previously, it was shown that attenuating protein synthesis downstream of the mechanistic target of rapamycin (mTOR) gradually increases expression of heat shock response (HSR) genes in a manner that correlates with increased resilience to protein unfolding stress. Here, we investigate the role of specific tissues in mediating the cytoprotective effects of low translation. METHODS: This study uses genetic tools (transgenic Caenorhabditis elegans (C. elegans), RNA interference and gene expression analysis) as well as physiological assays (survival and paralysis assays) in order to better understand how specific tissues contribute to adaptive changes involving cellular cross-talk that enhance proteostasis under low translation conditions. RESULTS: We use the C. elegans system to show that lowering translation in neurons or the germline increases heat shock gene expression and survival under conditions of heat stress. In addition, we find that low translation in these tissues protects motility in a body muscle-specific model of proteotoxicity that results in paralysis. Low translation in neurons or germline also results in increased expression of certain muscle regulatory and structural genes, reversing reduced expression normally observed with aging in C. elegans. Enhanced resilience to protein unfolding stress requires neuronal expression of cbp-1. CONCLUSIONS: Low translation in either neurons or the germline orchestrate protective adaptation in other tissues, including body muscle.


Asunto(s)
Proteínas de Caenorhabditis elegans , Caenorhabditis elegans , Respuesta al Choque Térmico , Biosíntesis de Proteínas , Proteostasis , Serina-Treonina Quinasas TOR , Animales , Animales Modificados Genéticamente , Caenorhabditis elegans/genética , Caenorhabditis elegans/metabolismo , Caenorhabditis elegans/fisiología , Proteínas de Caenorhabditis elegans/genética , Proteínas de Caenorhabditis elegans/metabolismo , Respuesta al Choque Térmico/genética , Neuronas/metabolismo , Interferencia de ARN , Serina-Treonina Quinasas TOR/metabolismo , Serina-Treonina Quinasas TOR/genética
10.
Viruses ; 16(7)2024 Jul 16.
Artículo en Inglés | MEDLINE | ID: mdl-39066302

RESUMEN

Mozambique introduced the Rotarix® vaccine into the National Immunization Program in September 2015. Following vaccine introduction, rotavirus A (RVA) genotypes, G9P[4] and G9P[6], were detected for the first time since rotavirus surveillance programs were implemented in the country. To understand the emergence of these strains, the whole genomes of 47 ELISA RVA positive strains detected between 2015 and 2018 were characterized using an Illumina MiSeq-based sequencing pipeline. Of the 29 G9 strains characterized, 14 exhibited a typical Wa-like genome constellation and 15 a DS-1-like genome constellation. Mostly, the G9P[4] and G9P[6] strains clustered consistently for most of the genome segments, except the G- and P-genotypes. For the G9 genotype, the strains formed three different conserved clades, separated by the P type (P[4], P[6] and P[8]), suggesting different origins for this genotype. Analysis of the VP6-encoding gene revealed that seven G9P[6] strains clustered close to antelope and bovine strains. A rare E6 NSP4 genotype was detected for strain RVA/Human-wt/MOZ/HCN1595/2017/G9P[4] and a genetically distinct lineage IV or OP354-like P[8] was identified for RVA/Human-wt/MOZ/HGJM0644/2015/G9P[8] strain. These results highlight the need for genomic surveillance of RVA strains detected in Mozambique and the importance of following a One Health approach to identify and characterize potential zoonotic strains causing acute gastroenteritis in Mozambican children.


Asunto(s)
Genoma Viral , Genotipo , Filogenia , Infecciones por Rotavirus , Vacunas contra Rotavirus , Rotavirus , Vacunas Atenuadas , Rotavirus/genética , Rotavirus/clasificación , Rotavirus/aislamiento & purificación , Vacunas contra Rotavirus/inmunología , Vacunas contra Rotavirus/administración & dosificación , Mozambique/epidemiología , Infecciones por Rotavirus/prevención & control , Infecciones por Rotavirus/virología , Infecciones por Rotavirus/epidemiología , Humanos , Vacunas Atenuadas/genética , Vacunas Atenuadas/inmunología , Secuenciación Completa del Genoma , Animales , Lactante , Preescolar , Proteínas de la Cápside/genética , Gastroenteritis/virología , Gastroenteritis/prevención & control , Gastroenteritis/epidemiología , Bovinos , Heces/virología
11.
Cureus ; 16(6): e62870, 2024 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-39040740

RESUMEN

Thrombophilias, which include both hereditary and acquired illnesses, are a range of abnormalities that make persons more prone to developing thromboembolism. Thrombophilic conditions carry significant dangers during pregnancy, such as miscarriage in early pregnancy, intrauterine growth restriction, abruptio placenta, and preeclampsia. According to compiled statistics, an average of 15%-20% of pregnancies end in miscarriage. While the risk of miscarriage in a first pregnancy is 11%, this risk increases to between 13% and 17% in subsequent pregnancies, and after the third miscarriage, it reaches 38%. This research article presents a detailed case report that focuses on a patient who has experienced three previous failed pregnancies. The patient's genetic analysis indicates that she has two copies of a mutated version of the methylenetetrahydrofolate reductase (MTHFR) gene (Ala222Val) and a variation in the plasminogen activator inhibitor 1 (PAI-1) gene known as 4G/5G. In addition, an evaluation of immunological characteristics revealed increased amounts of natural killer (NK) cells with enhanced activity, along with the identification of embryotoxins in a blood test that suppress embryotoxicity in a blood test, assisted by DNA isolation and real-time polymerase chain reaction (PCR) DNA analysis.

12.
Phytomedicine ; 132: 155792, 2024 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-39059090

RESUMEN

BACKGROUND: Numerous studies indicate that natural polysaccharides have immune-enhancing effects as a host defense potentiator. Few reports are available on hormetic effects of natural polysaccharides, and the underlying mechanisms remain unclear. PURPOSE: AELP-B6 (arabinose- and galactose-rich pectin polysaccharide) from Aralia elata (Miq.) Seem was taken as a case study to clarify the potential mechanism of hormetic effects of natural polysaccharides. METHODS: The pharmacodynamic effect of AELP-B6 was verified by constructing the CTX-immunosuppressive mouse model. The hormetic effects were explored by TMT-labeled proteomics, energy metabolism analysis, flow cytometry and western blot. The core-affinity target of AELP-B6 was determined by pull down, nanoLC-nanoESI+-MS, CETSA, immunoblot and SPR assay. The RAW264.7Clec4G-RFP and RAW264.7Rab1A-RFP cell lines were simultaneously constructed to determine the affinity difference between AELP-B6 and targets by confocal laser scanning live-cell imaging. Antibody blocking assays were further used to verify the mechanism of hormetic effects. RESULTS: AELP-B6 at low and medium doses may maintain the structural integrity of thymus and spleen, increase the concentrations of TNF-α, IFN-γ, IL-3 and IL-8, and alleviate CTX-induced reduction of immune cell viability in vivo. Proteomics and energy metabolism analysis revealed that AELP-B6 regulate HIF-1α-mediated metabolic programming, causing Warburg effects in macrophages. AELP-B6 at low and medium doses promoted the release of intracellular immune factors, and driving M1-like polarization of macrophages. As a contrast, AELP-B6 at high dose enhanced the expression levels of apoptosis related proteins, indicating activation of the intrinsic apoptotic cascade. Two highly expressed transmembrane proteins in macrophages, Clec4G and Rab1A, were identified as the primary binding targets of AELP-B6 which co-localized with the cell membrane and directly impacted with immune cell activation and apoptosis. AELP-B6 exhibits affinity differences with Clec4G and Rab1A, which is the key to the hormetic effects. CONCLUSION: We observed hormesis of natural polysaccharide (AELP-B6) for the first time, and AELP-B6 mediates the hormetic effects through two dose-related targets. Low dose of AELP-B6 targets Clec4G, thereby driving the M1-like polarization via regulating NF-κB signaling pathway and HIF-1α-mediated metabolic programming, whereas high dose of AELP-B6 targets Rab1A, leading to mitochondria-dependent apoptosis.


Asunto(s)
Pectinas , Animales , Ratones , Pectinas/farmacología , Lectinas Tipo C/metabolismo , Células RAW 264.7 , Metabolismo Energético/efectos de los fármacos , Polisacáridos/farmacología
13.
Environ Geochem Health ; 46(8): 302, 2024 Jul 11.
Artículo en Inglés | MEDLINE | ID: mdl-38990227

RESUMEN

In this study, a highly efficient CoFe2O4-anchored g-C3N4 nanocomposite with Z-scheme photocatalyst was developed by facile calcination and hydrothermal technique. To evaluate the crystalline structure, sample surface morphology, elemental compositions, and charge conductivity of the as-synthesized catalysts by various characterization techniques. The high interfacial contact of CoFe2O4 nanoparticles (NPs) with g-C3N4 nanosheets reduced the optical bandgap from 2.67 to 2.5 eV, which improved the charge carrier separation and transfer. The photo-degradation of methylene blue (MB) and rhodamine B (Rh B) aqueous pollutant suspension under visible-light influence was used to investigate the photocatalytic degradation activity of the efficient CoFe2O4/g-C3N4 composite catalyst. The heterostructured spinel CoFe2O4 anchored g-C3N4 photocatalysts (PCs) with Z-scheme show better photocatalytic degradation performance for both organic dyes. Meanwhile, the efficiency of aqueous MB and Rh B degradation in 120 and 100 min under visible-light could be up to 91.1% and 73.7%, which is greater than pristine g-C3N4 and CoFe2O4 catalysts. The recycling stability test showed no significant changes in the photo-degradation activity after four repeated cycles. Thus, this work provides an efficient tactic for the construction of highly efficient magnetic PCs for the removal of hazardous pollutants in the aquatic environment.


Asunto(s)
Cobalto , Compuestos Férricos , Azul de Metileno , Nanocompuestos , Rodaminas , Contaminantes Químicos del Agua , Cobalto/química , Compuestos Férricos/química , Catálisis , Nanocompuestos/química , Rodaminas/química , Contaminantes Químicos del Agua/química , Azul de Metileno/química , Fotólisis , Luz , Compuestos Inorgánicos de Carbono/química , Nitrilos/química , Procesos Fotoquímicos , Compuestos de Nitrógeno/química , Grafito
14.
Sensors (Basel) ; 24(11)2024 May 28.
Artículo en Inglés | MEDLINE | ID: mdl-38894257

RESUMEN

In the face of rising population, erratic climate, resource depletion, and increased exposure to natural hazards, environmental monitoring is increasingly important. Satellite data form most of our observations of Earth. On-the-ground observations based on in situ sensor systems are crucial for these remote measurements to be dependable. Providing open-source options to rapidly prototype environmental datalogging systems allows quick advancement of research and monitoring programs. This paper introduces Loom, a development environment for low-power Arduino-programmable microcontrollers. Loom accommodates a range of integrated components including sensors, various datalogging formats, internet connectivity (including Wi-Fi and 4G Long Term Evolution (LTE)), radio telemetry, timing mechanisms, debugging information, and power conservation functions. Additionally, Loom includes unique applications for science, technology, engineering, and mathematics (STEM) education. By establishing modular, reconfigurable, and extensible functionality across components, Loom reduces development time for prototyping new systems. Bug fixes and optimizations achieved in one project benefit all projects that use Loom, enhancing efficiency. Although not a one-size-fits-all solution, this approach has empowered a small group of developers to support larger multidisciplinary teams designing diverse environmental sensing applications for water, soil, atmosphere, agriculture, environmental hazards, scientific monitoring, and education. This paper not only outlines the system design but also discusses alternative approaches explored and key decision points in Loom's development.

15.
Vaccines (Basel) ; 12(6)2024 Jun 08.
Artículo en Inglés | MEDLINE | ID: mdl-38932372

RESUMEN

Sublingual vaccines offer the benefits of inducing mucosal immunity to protect against respiratory viruses, including Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) and influenza, while also enabling needle-free self-administration. In a previous study, a sublingual SARS-CoV-2 vaccination was created by combining a recombinafigureCoV-2 spike protein receptor-binding domain antigen with a double strand RNA Poly(I:C) adjuvant. This vaccine was tested on nonhuman primates, Cynomolgus macaques. This study examined the immune and inflammatory responses elicited by the sublingual influenza vaccine containing hemagglutinin (HA) antigen and Poly(I:C) adjuvants, and assessed the safety of this vaccine in nonhuman primates. The Poly(I:C)-adjuvanted sublingual vaccine induced both mucosal and systemic immunities. Specifically, the sublingual vaccine produced HA-specific secretory IgA antibodies in saliva and nasal washings, and HA-specific IgA and IgG were detected in the blood. This vaccine appeared to be safe, as judged from the results of blood tests and plasma C-reactive protein levels. Notably, sublingual vaccination neither increased the production of inflammation-associated cytokines-IFN-alpha, IFN-gamma, and IL-17-in the blood, nor upregulated the gene expression of proinflammatory cytokines-IL12A, IL12B, IFNA1, IFNB1, CD69, and granzyme B-in white blood cells. Moreover, DNA microarray analyses revealed that sublingual vaccination evoked both enhancing and suppressing expression changes in genes associated with immune-related responses in cynomolgus monkeys. Therefore, the sublingual vaccine with the Poly(I:C) adjuvant is safe, and creates a balanced state of enhancing and suppressing the immune-related response.

16.
Immunol Lett ; 268: 106887, 2024 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-38925442

RESUMEN

Vaccines and antibodies that specifically target or neutralize components of the SARS-CoV-2 virus are effective in prevention and treatment of human patients with SARS-CoV-2 infection. However, vaccines and SARS-CoV-2 neutralization antibodies target a subset of epitopes of viral proteins, and the fast evolution of the SARS-CoV-2 virus and the continuing emergence of SARS-CoV-2 variants confer SARS-CoV-2 immune escape from these therapies. ACE2 is the human cell receptor that serves as the entry point for SARS-CoV-2 into human cells and thus is the gatekeeper for SARS-CoV-2 infection of humans. We report here the development of 4G8C11, an anti-human ACE2 receptor monoclonal antibody that recognizes ACE2 on human cell surfaces. We determined that 4G8C11 blocks SARS-CoV-2 and variant infection of ACE2+ human cells. Furthermore, 4G8C11 has minimal effects on ACE2 receptor activity. 4G8C11 is therefore a monoclonal antibody for ACE2 receptor detection and potentially an effective immunotherapeutic agent for SARS-CoV-2 and variants.


Asunto(s)
Enzima Convertidora de Angiotensina 2 , Anticuerpos Monoclonales , Anticuerpos Neutralizantes , Anticuerpos Antivirales , COVID-19 , SARS-CoV-2 , Humanos , Enzima Convertidora de Angiotensina 2/metabolismo , Enzima Convertidora de Angiotensina 2/inmunología , SARS-CoV-2/inmunología , COVID-19/inmunología , Anticuerpos Monoclonales/farmacología , Anticuerpos Monoclonales/inmunología , Anticuerpos Monoclonales/uso terapéutico , Anticuerpos Antivirales/inmunología , Anticuerpos Neutralizantes/inmunología , Internalización del Virus/efectos de los fármacos , Células HEK293 , Animales , Chlorocebus aethiops
17.
Environ Res ; 258: 119484, 2024 Oct 01.
Artículo en Inglés | MEDLINE | ID: mdl-38914250

RESUMEN

The present research utilizes a sol-gel approach to create a CoFe2O4/g-C3N4 nanocomposite (NC) and explored several analytical methods to evaluate physical, chemical and optical based characteristics via XRD, FTIR, UV-vis, SEM/EDS and XPS for the prepared pure CoFe2O4, g-C3N4, and CoFe2O4/g-C3N4 NC. The XRD results show that the prepared g-C3N4, CoFe2O4, exhibits hexagonal and cubic phases respectively, whereas the g-C3N4/CoFe2O4 NC exhibit mixing of two phases. The energy band gaps for pure g-C3N4, CoFe2O4 and g-C3N4/CoFe2O4 NC values are viz., 2.75, 1.3, and 2.4 eV. As photocatalysts, synthesized materials were utilized for the decomposition of Rhodamine-B (RhB) dye. Finally, the CoFe2O4/g-C3N4 NC showed good performance of photocatalysis for RhB dye disintegration under the stimulus of visible light. According to the induced visible light, the rate at which the photocatalytic degradation occurs for the CoFe2O4/g-C3N4 NC was found to be 57% in 120 min and this is greater when compared with pure catalysts like CoFe2O4 (28%) and g-C3N4 (10%). These outcomes suggest that the prepared NC have efficiently worked during the photocatalytic process compared with its pure materials.


Asunto(s)
Cobalto , Compuestos Férricos , Grafito , Rodaminas , Cobalto/química , Rodaminas/química , Compuestos Férricos/química , Grafito/química , Compuestos de Nitrógeno/química , Fotólisis , Nanocompuestos/química , Catálisis , Nitrilos/química
18.
Int J Mol Sci ; 25(9)2024 Apr 24.
Artículo en Inglés | MEDLINE | ID: mdl-38731839

RESUMEN

CLEC4G, a glycan-binding receptor, has previously been demonstrated to inhibit Aß generation, yet its brain localization and functions in Alzheimer's disease (AD) are not clear. We explored the localization, function, and regulatory network of CLEC4G via experiments and analysis of RNA-seq databases. CLEC4G transcripts and proteins were identified in brain tissues, with the highest expression observed in neurons. Notably, AD was associated with reduced levels of CLEC4G transcripts. Bioinformatic analyses revealed interactions between CLEC4G and relevant genes such as BACE1, NPC1, PILRA, TYROBP, MGAT1, and MGAT3, all displaying a negative correlation trend. We further identified the upstream transcriptional regulators NR2F6 and XRCC4 for CLEC4G and confirmed a decrease in CLEC4G expression in APP/PS1 transgenic mice. This study highlights the role of CLEC4G in protecting against AD progression and the significance of CLEC4G for AD research and management.


Asunto(s)
Enfermedad de Alzheimer , Lectinas Tipo C , Ratones Transgénicos , Neuronas , Enfermedad de Alzheimer/metabolismo , Enfermedad de Alzheimer/genética , Enfermedad de Alzheimer/patología , Animales , Neuronas/metabolismo , Ratones , Humanos , Lectinas Tipo C/metabolismo , Lectinas Tipo C/genética , Encéfalo/metabolismo , Encéfalo/patología , Regulación de la Expresión Génica , Modelos Animales de Enfermedad
19.
Heliyon ; 10(10): e31221, 2024 May 30.
Artículo en Inglés | MEDLINE | ID: mdl-38813157

RESUMEN

In this novel research, S-scheme Ag2CrO4/g-C3N4 heterojunctions were generated by sonochemical hybridization of different compositions of Ag2CrO4 nanoparticles [EVB = +2.21 eV] and g-C3N4 sheets [ECB = -1.3 eV] for destructing RhB dye under artificial solar radiation. The as-synthesized nanocomposites were subjected to X-ray diffraction [XRD], diffuse reflectance spectrum [DRS], X-ray photoelectron spectroscopy [XPS], N2-adsorption-desorption isotherm, photoluminescence [PL] and high resolution transmission electron microscope [HRTEM] analysis to explore the interfacial interactions between g-C3N4 sheets and Ag2CrO4 nanoparticles. Spherical Ag2CrO4 nanoparticles deposited homogeneously on the wrinkles points of g-C3N4 sheets at nearly equidistant from each other facilitating the uniform absorption of solar radiations. The absorbability of solar radiations was enhanced by introducing 20 wt % Ag2CrO4 on g-C3N4 sheets. The surface area of g-C3N4 sheets was reduced from 37.5 to 16.4 m2/g and PL signal intensity diminished by 80 % implying the successful interfacial interaction between Ag2CrO4 nanoparticles and g-C3N4 sheets. The photocatalytic performance of heterojunctions containing 20 % Ag2CrO4 and 80 % g-C3N4 destructed 96 % of RhB dye compared with 60 and 33 % removal on the surface of pristine g-C3N4 sheets and Ag2CrO4, respectively. Benzoquinone and ammonium oxalate are strongly scavenged the dye decomposition revealing the strong influence of valence band holes of Ag2CrO4 and superoxide radicals in destructing RhB dye under solar radiations. S-scheme charge transportation mechanism was suggested rather than type II heterojunction on the light of scavenger trapping experiments results and PL spectrum of terephthalic acid. Overall, this research work illustrated the manipulation of novel S-scheme heterojunction with efficient redox power for destructing various organic pollutants persisted in water resources.

20.
J Econ Entomol ; 117(4): 1665-1674, 2024 Aug 12.
Artículo en Inglés | MEDLINE | ID: mdl-38783401

RESUMEN

Cytochrome P450 (CYP) 4G subfamily is closely related to the synthesis of cuticular hydrocarbons, leading to the enhanced desiccation and insecticide resistance of pests. However, functions of CYP4Gs in larval integument development remain unknown in Spodoptera frugiperda (J. E. Smith) (Lepidoptera: Noctuidae), which is a major transboundary migratory pest and become a common pest in China. On the basis of the genome and transcriptome datasets of S. frugiperda, CYP4G74, CYP4G75, CYP4G108, and CYP4G109 were identified, which contained the conserved domains of P450s and CYP4Gs. The spatial and temporal expression analysis showed that CYP4G74 and CYP4G75 were significantly highly expressed in adults and larval integuments, while CYP4G108 and CYP4G109 had low expressions in larval integuments. After silencing CYP4G74 and CYP4G75 by RNA interference, abnormal integument development occurred in larvae, some of which became smaller and dead, indicating important roles of CYP4G74 and CYP4G75 in the synthesis and development of integuments. The results clarify the functions of CYP4Gs in S. frugiperda and provide potential targets for the control of this pest.


Asunto(s)
Proteínas de Insectos , Integumento Común , Larva , Spodoptera , Animales , Spodoptera/genética , Spodoptera/crecimiento & desarrollo , Larva/crecimiento & desarrollo , Larva/genética , Proteínas de Insectos/genética , Proteínas de Insectos/metabolismo , Interferencia de ARN , Sistema Enzimático del Citocromo P-450/genética , Sistema Enzimático del Citocromo P-450/metabolismo
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