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1.
Front Pharmacol ; 15: 1415352, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-39092222

RESUMO

Introduction: Natural plants are valuable resources for exploring new bioactive compounds. Artemisia vulgaris L. is a traditional Chinese medicinal herb that has been historically used for treating multiple diseases. Active compounds isolated and extracted from A. vulgaris L. typically possess immunomodulatory and anti-inflammatory properties. Artemvulactone E (AE) is a new sesquiterpene lactone isolated and extracted from A. vulgaris L. with unclear biological activities. Methods: The immunoregulatory effects of AE on macrophages were assessed by ELISA, RT-qPCR, immunofluorescence, and western blot assay. The effect of AE on lipopolysaccharide (LPS) -relates signaling pathways was examined by western blot assay. In zebrafish models, the larvae were yolk-microinjected with LPS to establish inflammation model and the effect of AE was evaluated by determining the survival rate, heart rate, yolk sac edema size, neutrophils and macrophages infiltration of zebrafish. The interaction between AE and Toll-like receptor 4 (TLR4) was examined by molecular docking and dynamic stimulation. Results: AE reduced the expression and secretion of pro-inflammatory cytokines (TNF-α and IL-6), inflammatory mediators iNOS and COX-2, as well as decreases the production of intracellular NO and ROS in LPS-stimulated macrophages. In addition, AE exerted its anti-inflammatory effect synergistically by inhibiting MAPK/JAK/STAT3-NF-κB signaling pathways. Furthermore, AE enhanced the survival rate and attenuated inflammatory response in zebrafish embryos treated with LPS. Finally, the molecular dynamics results indicate that AE forms stable complexes with LPS receptor TLR4 through the Ser127 residue, thus completely impairing the subsequent activation of MAPK-NF-κB signaling. Conclusion: AE exhibits notable anti-inflammatory activity and represents as a potential agent for treating inflammation-associated diseases.

2.
Int J Biol Macromol ; : 134815, 2024 Aug 16.
Artigo em Inglês | MEDLINE | ID: mdl-39154690

RESUMO

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.
J Adv Res ; 2024 Aug 03.
Artigo em Inglês | MEDLINE | ID: mdl-39103048

RESUMO

INTRODUCTION: Mitophagy, a selective form of autophagy responsible for maintaining mitochondrial homeostasis, regulates the antiviral immune response and acts as viral replication platforms to facilitate infection with various viruses. However, its precise role in herpes simplex virus 1 (HSV-1) infection and herpes simplex encephalitis (HSE) remains largely unknown. OBJECTIVES: We aimed to investigate the regulation of mitophagy by HSV-1 neurotropic infection and its role in viral encephalitis, and to identify small compounds that regulate mitophagy to affect HSV-1 infection. METHODS: The antiviral effects of compounds were investigated by Western blot, RT-PCR and plaque assay. The changes of Parkin (PRKN)-mediated mitophagy and Nuclear Factor kappa B (NFKB)-mediated neuroinflammation were examined by TEM, RT-qPCR, Western blot and ELISA. The therapeutic effect of taurine or PRKN-overexpression was confirmed in the HSE mouse model by evaluating survival rate, eye damage, neurodegenerative symptoms, immunohistochemistry analysis and histopathology. RESULTS: HSV-1 infection caused the accumulation of damaged mitochondria in neuronal cells and in the brain tissue of HSE mice. Early HSV-1 infection led to mitophagy activation, followed by inhibition in the later viral infection. The HSV-1 proteins ICP34.5 or US11 deregulated the EIF2S1-ATF4 axis to suppress PRKN/Parkin mRNA expression, thereby impeding PRKN-dependent mitophagy. Consequently, inhibition of mitophagy by specific inhibitor midiv-1 promoted HSV-1 infection, whereas mitophagy activation by PRKN overexpression or agonists (CCCP and rotenone) attenuated HSV-1 infection and reduced the NF-κB-mediated neuroinflammation. Moreover, PRKN-overexpressing mice showed enhanced resistance to HSV-1 infection and ameliorated HSE pathogenesis. Furthermore, taurine, a differentially regulated gut microbial metabolite upon HSV-1 infection, acted as a mitophagy activator that transcriptionally promotes PRKN expression to stimulate mitophagy and to limit HSV-1 infection both in vitro and in vivo. CONCLUSION: These results reveal the protective function of mitophagy in HSE pathogenesis and highlight mitophagy activation as a potential antiviral therapeutic strategy for HSV-1-related diseases.

4.
Microsc Res Tech ; 2024 Jul 27.
Artigo em Inglês | MEDLINE | ID: mdl-39072964

RESUMO

Cotesia gregalis Yang et Wei (Hymenoptera: Braconidae) is a gregarious koinobiont endoparasitic wasp attacking the larvae of fall webworm, Hyphantria cunea, an important invasive insect pest in China. To better understand the parasitic wasps' mating and parasitic behaviors, we examined the morphology of the antennae of adult C. gregalis, as well as the type, number, and distribution of antennal sensilla, via scanning electron microscopy. The antennae of female and male C. gregalis are filiform and comprise a scape, pedicel, and 16 flagellomeres. The female antennae are significantly shorter than those of male. A total of nine morphological types of antennal sensilla (mechanoreceptor and chemoreceptor) are presented in both sexes, including four mechanoreceptors (sensilla chaetica [two subtypes], sensilla trichodea and Böhm bristles); five chemoreceptors (sensilla basiconica [two subtypes], sensilla placodea, sensilla styloconica, and sensilla coelocapitula). There is no difference in the type and distribution of antennal sensilla between males and females, but the number and length of some antennal sensilla show sexual dimorphism. The functional morphology of the sensilla of C. gregalis is discussed by comparison with other parasitic wasps. These findings provide foundation for further research on the chemical communication and host localization mechanisms of C. gregalis. RESEARCH HIGHLIGHTS: The first report of morphology and distribution pattern of the antennal sensilla in C. gregalis is discussed. A total of seven main types and nine antennal sensilla subtypes are observed in male and female C. gregalis. The type and distribution of antennal sensilla in males and females are identical; however, the number and length of certain antennal sensilla show sexual dimorphism.

5.
BMC Complement Med Ther ; 24(1): 264, 2024 Jul 11.
Artigo em Inglês | MEDLINE | ID: mdl-38992644

RESUMO

BACKGROUND: Artemisia argyi is a traditional herbal medicine belonging to the genus Artemisia that plays an important role in suppressing inflammation. However, the chemical constituents and underlying mechanisms of its therapeutic potential in neuroinflammation are still incompletely understood, and warrant further investigation. METHODS: Several column chromatography were employed to isolate and purify chemical constituents from Artemisia argyi, and modern spectroscopy techniques were used to elucidate their chemical structures. The screening of monomeric compounds with nitric oxide inhibition led to the identification of the most effective bioactive compound, which was subsequently confirmed for its anti-inflammatory capability through qRT‒PCR. Predictions of compound-target interactions were made using the PharmMapper webserver and the TargetNet database, and an integrative protein-protein interaction network was constructed by intersecting the predicted targets with neuroinflammation-related targets. Topological analysis was performed to identify core targets, and molecular docking and molecular dynamics simulations were utilized to validate the findings. The result of the molecular simulations was experimentally validated through drug affinity responsive target stability (DARTS) and Western blot experiments. RESULTS: Seventeen sesquiterpenoids, including fifteen known sesquiterpenoids and two newly discovered guaiane-type sesquiterpenoids (argyinolide S and argyinolide T) were isolated from Artemisia argyi. Bioactivity screening revealed that argyinolide S (AS) possessed the most potent anti-inflammatory activity. However, argyinolide T (AT) showed weak anti-inflammatory activity, so AS was the target compound for further study. AS may regulate neuroinflammation through its modulation of eleven core targets: protein kinase B 1 (AKT1), epidermal growth factor receptor (EGFR), proto-oncogene tyrosine-protein Kinase (FYN), Janus Kinase (JAK) 1, mitogen-activated protein (MAP) Kinase 1,8 and 14, matrix metalloproteinase 9 (MMP9), ras-related C3 botulinum toxin substrate 1 (RAC1), nuclear factor kappa-B p65 (RELA), and retinoid X receptor alpha (RXRA). Molecular dynamics simulations and DARTS experiments confirmed the stable binding of AS to JAK1, and Western blot experiments demonstrated the ability of AS to inhibit the phosphorylation of downstream Signal transducer and activator of transcription 3 (STAT3) mediated by JAK1. CONCLUSIONS: The sesquiterpenoid compounds isolated from Artemisia argyi, exhibit significant inhibitory effects on inflammation in C57BL/6 murine microglia cells (BV-2). Among these compounds, AS, a newly discovered guaiane-type sesquiterpenoid in Artemisia argyi, has been demonstrated to effectively inhibit the occurrence of neuroinflammation by targeting JAK1.


Assuntos
Anti-Inflamatórios , Artemisia , Simulação de Acoplamento Molecular , Sesquiterpenos , Artemisia/química , Animais , Sesquiterpenos/farmacologia , Sesquiterpenos/química , Camundongos , Anti-Inflamatórios/farmacologia , Anti-Inflamatórios/química , Extratos Vegetais/farmacologia , Extratos Vegetais/química , Células RAW 264.7 , Doenças Neuroinflamatórias/tratamento farmacológico , Simulação de Dinâmica Molecular
6.
Int J Biol Macromol ; 273(Pt 1): 133032, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38862053

RESUMO

Collagen's unique properties promise hemostatic potential, but its sponge form's stability and mechanics need improvement. In this study, we developed a series of homeostatic sponges by co-assembling collagen and curdlan at different ratios into hydrogels, followed by freeze-drying treatment. The incorporation of curdlan into collagen sponges has been found to significantly enhance the sponge's properties, including increased porosity, elevated water uptake, improved elasticity, and enhanced resistance to degradation. In vitro cytotoxicity and hemolysis assays have demonstrated the biocompatibility and nontoxicity of composite sponges. In mouse liver perforation and incision models, the composite sponges achieved rapid coagulation within 67 s and 75 s, respectively, outperforming gauze and gelatin sponge in reducing blood loss. Furthermore, composite sponges demonstrated superior wound healing potential in mice full-thickness skin defects model, with accelerated healing rates observed at days 3, 7, and 14 compared to the control group. Overall, collagen/curdlan composite sponge show promise for hemostasis and wound healing applications.


Assuntos
Colágeno , Hemostasia , Cicatrização , beta-Glucanas , Animais , Cicatrização/efeitos dos fármacos , Colágeno/química , Colágeno/farmacologia , beta-Glucanas/farmacologia , beta-Glucanas/química , Camundongos , Hemostasia/efeitos dos fármacos , Pele/efeitos dos fármacos , Pele/lesões , Hidrogéis/química , Hidrogéis/farmacologia , Hemólise/efeitos dos fármacos , Hemostáticos/farmacologia , Hemostáticos/química , Porosidade , Materiais Biocompatíveis/química , Materiais Biocompatíveis/farmacologia , Humanos , Masculino
7.
Adv Sci (Weinh) ; : e2309307, 2024 Jun 25.
Artigo em Inglês | MEDLINE | ID: mdl-38923329

RESUMO

Glaucoma is a leading cause of irreversible blindness worldwide and is characterized by progressive retinal ganglion cell (RGC) degeneration and vision loss. Since irreversible neurodegeneration occurs before diagnosable, early diagnosis and effective neuroprotection are critical for glaucoma management. Small extracellular vesicles (sEVs) are demonstrated to be potential novel biomarkers and therapeutics for a variety of diseases. In this study, it is found that intravitreal injection of circulating plasma-derived sEVs (PDEV) from glaucoma patients ameliorated retinal degeneration in chronic ocular hypertension (COH) mice. Moreover, it is found that PDEV-miR-29s are significantly upregulated in glaucoma patients and are associated with visual field defects in progressed glaucoma. Subsequently, in vivo and in vitro experiments are conducted to investigate the possible function of miR-29s in RGC pathophysiology. It is showed that the overexpression of miR-29b-3p effectively prevents RGC degeneration in COH mice and promotes the neuronal differentiation of human induced pluripotent stem cells (hiPSCs). Interestingly, engineered sEVs with sufficient miR-29b-3p delivery exhibit more effective RGC protection and neuronal differentiation efficiency. Thus, elevated PDEV-miR-29s may imply systemic regulation to prevent RGC degeneration in glaucoma patients. This study provides new insights into PDEV-based glaucoma diagnosis and therapeutic strategies for neurodegenerative diseases.

8.
Sci Rep ; 14(1): 12651, 2024 06 02.
Artigo em Inglês | MEDLINE | ID: mdl-38825618

RESUMO

Effective disinfection methods are crucial in the cold chain transportation process of food due to the specificity of temperature and the diversity of contaminated flora. The objective of this study was to investigate the sanitizing effect of different disinfectants on various fungi at - 20 °C to achieve accurate disinfection of diverse bacterial populations. Peracetic acid, hydrogen peroxide, and potassium bisulfate were selected as low-temperature disinfectants and were combined with antifreeze. The sanitizing effect of these cryogenic disinfectants on pathogens such as Bacillus subtilis black variant spores (ATCC9372), Staphylococcus aureus (ATCC 6538), Candida albicans (ATCC 10231), Escherichia coli (8099), and poliovirus (PV-1) was sequentially verified by bactericidal and virus inactivation experiments. After a specified time of disinfection, a neutralizing agent was used to halt the sanitizing process. The study demonstrates that different disinfectants exhibit selective effects during the low-temperature disinfection process. Peracetic acid, hydrogen peroxide, and potassium monopersulfate are suitable for the low-temperature environmental disinfection of bacterial propagules, viruses, and fungal contaminants. However, for microorganisms with strong resistance to spores, a low-temperature disinfectant based on peracetic acid should be chosen for effective disinfection treatment. Our results provide a valuable reference for selecting appropriate disinfectants to sanitize various potential pathogens in the future.


Assuntos
Temperatura Baixa , Desinfetantes , Desinfecção , Peróxido de Hidrogênio , Ácido Peracético , Desinfetantes/farmacologia , Desinfecção/métodos , Peróxido de Hidrogênio/farmacologia , Ácido Peracético/farmacologia , Sulfatos/farmacologia , Bacillus subtilis/efeitos dos fármacos , Compostos de Potássio/farmacologia , Staphylococcus aureus/efeitos dos fármacos , Candida albicans/efeitos dos fármacos , Escherichia coli/efeitos dos fármacos , Poliovirus/efeitos dos fármacos
9.
BMC Pregnancy Childbirth ; 24(1): 371, 2024 May 15.
Artigo em Inglês | MEDLINE | ID: mdl-38750445

RESUMO

BACKGROUND: To explore a method for screening and diagnosing neonatal congenital heart disease (CHD) applicable to grassroots level, evaluate the prevalence of CHD, and establish a hierarchical management system for CHD screening and treatment at the grassroots level. METHODS: A total of 24,253 newborns born in Tang County between January 2016 and December 2020 were consecutively enrolled and screened by trained primary physicians via the "twelve-section ultrasonic screening and diagnosis method" (referred to as the "twelve-section method"). Specialized staff from the CHD Screening and Diagnosis Center of Hebei Children's Hospital regularly visited the local area for definite diagnosis of CHD in newborns who screened positive. Newborns with CHD were managed according to the hierarchical management system. RESULTS: The centre confirmed that, except for 2 newborns with patent ductus arteriosus missed in the diagnosis of ventricular septal defect combined with severe pulmonary hypertension, newborns with other isolated or concomitant simple CHDs were identified at the grassroots level. The sensitivity, specificity and diagnostic coincidence rate of the twelve-section method for screening complex CHD were 92%, 99.6% and 84%, respectively. A total of 301 children with CHD were identified. The overall CHD prevalence was 12.4‰. According to the hierarchical management system, 113 patients with simple CHD recovered spontaneously during local follow-up, 48 patients continued local follow-up, 106 patients were referred to the centre for surgery (including 17 patients with severe CHD and 89 patients with progressive CHD), 1 patient died without surgery, and 8 patients were lost to follow-up. Eighteen patients with complex CHD were directly referred to the centre for surgery, 3 patients died without surgery, and 4 patients were lost to follow-up. Most patients who received early intervention achieved satisfactory results. The mortality rate of CHD was approximately 28.86 per 100,000 children. CONCLUSIONS: The "twelve-section method" is suitable for screening neonatal CHD at the grassroots level. The establishment of a hierarchical management system for CHD screening and treatment is conducive to the scientific management of CHD, which has important clinical and social significance for early detection, early intervention, reduction in mortality and improvement of the prognosis of complex and severe CHDs.


Assuntos
Cardiopatias Congênitas , Triagem Neonatal , Humanos , Cardiopatias Congênitas/epidemiologia , Cardiopatias Congênitas/diagnóstico por imagem , Recém-Nascido , China/epidemiologia , Triagem Neonatal/métodos , Feminino , Masculino , Prevalência , Sensibilidade e Especificidade
10.
Biochem Biophys Res Commun ; 718: 149983, 2024 Jul 23.
Artigo em Inglês | MEDLINE | ID: mdl-38718735

RESUMO

Transmembrane 6 superfamily 1 (TM6SF1) is lowly expressed in lung adenocarcinoma (LUAD), but the function and mechanisms of TM6SF1 remain unclear. Thus, we attempt to explore the function of TM6SF1 and its underlying mechanisms in LUAD. qRT-PCR was used for detecting TM6SF1 mRNA expression. Immunohistochemistry staining was used for detecting the expression of MMP-2, TM6SF1, Ki67, MMP-9, and CD163 proteins. E-cadherin, p-PI3K, Vimentin, AKT, N-cadherin, PI3K, p-AKT, mTOR, p-mTOR, and marker proteins of M2 macrophages were evaluated using Western blot. CD206 protein expression was examined via immunofluorescence. The IL-10 concentration was measured via enzyme-linked immunosorbent assay (ELISA). Using CCK-8, colony formation and transwell assays, cell proliferation, migration, and invasion were assessed. A549 cells were injected into the mice's flank for establishing a mouse tumor model and into the tail vein for establishing the lung metastasis model. HE staining was performed to detect pathological changes in lung tissues. Decreased TM6SF1 expression was found in LUAD tissues and cells. TM6SF1 overexpression inhibited cell viability, proliferation, invasion, migration, EMT, and polarization of M2 macrophages in LUAD cells, along with tumor growth and metastasis in xenograft mice. Bioinformatics analysis demonstrated that TM6SF1 was correlated with the tumor microenvironment. TM6SF1 overexpression reduced expression levels of p-mTOR, p-PI3K, p-AKT, mTOR, and AKT. TM6SF1-caused inhibition of proliferation, migration, invasion and EMT, as M2 macrophage polarization was reversed by the PI3K activator in LUAD cells. TM6SF1 inactivated the PI3K/AKT/mTOR pathway to suppress LUAD malignancy and polarization of M2 macrophages, providing insight for developing new LUAD treatments.


Assuntos
Adenocarcinoma de Pulmão , Neoplasias Pulmonares , Macrófagos , Fosfatidilinositol 3-Quinases , Proteínas Proto-Oncogênicas c-akt , Transdução de Sinais , Serina-Treonina Quinases TOR , Animais , Humanos , Camundongos , Células A549 , Adenocarcinoma de Pulmão/patologia , Adenocarcinoma de Pulmão/metabolismo , Adenocarcinoma de Pulmão/genética , Movimento Celular , Proliferação de Células , Progressão da Doença , Neoplasias Pulmonares/patologia , Neoplasias Pulmonares/metabolismo , Neoplasias Pulmonares/genética , Ativação de Macrófagos/genética , Macrófagos/metabolismo , Macrófagos/patologia , Camundongos Endogâmicos BALB C , Camundongos Nus , Fosfatidilinositol 3-Quinases/metabolismo , Proteínas Proto-Oncogênicas c-akt/metabolismo , Serina-Treonina Quinases TOR/metabolismo
11.
Int Immunopharmacol ; 132: 111934, 2024 May 10.
Artigo em Inglês | MEDLINE | ID: mdl-38574701

RESUMO

PD-1/PD-L1 blockade therapy has brought great success to cancer treatment. Nevertheless, limited beneficiary populations and even hyperprogressive disease (HPD) greatly constrain the application of PD-1/PD-L1 inhibitors in clinical treatment. HPD is a special pattern of disease progression with rapid tumor growth and even serious consequences of patient death, which requires urgent attention. Among the many predisposing causes of HPD, regulatory T cells (Tregs) are suspected because they are amplified in cases of HPD. Tregs express PD-1 thus PD-1/PD-L1 blockade therapy may have an impact on Tregs which leads to HPD. Tregs are a subset of CD4+ T cells expressing FoxP3 and play critical roles in suppressing immunity. Tregs migrate toward tumors in the presence of chemokines to suppress antitumor immune responses, causing cancer cells to grow and proliferate. Studies have shown that deleting Tregs could enhance the efficacy of PD-1/PD-L1 blockade therapy and reduce the occurrence of HPD. This suggests that immunotherapy combined with Treg depletion may be an effective means of avoiding HPD. In this review, we summarized the immunosuppressive-related functions of Tregs in antitumor therapy and focused on advances in therapy combining Tregs depletion with PD-1/PD-L1 blockade in clinical studies. Moreover, we provided an outlook on Treg-targeted HPD early warning for PD-1/PD-L1 blockade therapy.


Assuntos
Antígeno B7-H1 , Progressão da Doença , Inibidores de Checkpoint Imunológico , Neoplasias , Receptor de Morte Celular Programada 1 , Linfócitos T Reguladores , Animais , Humanos , Antígeno B7-H1/antagonistas & inibidores , Antígeno B7-H1/imunologia , Inibidores de Checkpoint Imunológico/uso terapêutico , Imunoterapia/métodos , Neoplasias/imunologia , Neoplasias/tratamento farmacológico , Neoplasias/terapia , Receptor de Morte Celular Programada 1/antagonistas & inibidores , Receptor de Morte Celular Programada 1/imunologia , Linfócitos T Reguladores/imunologia , Linfócitos T Reguladores/efeitos dos fármacos
12.
Transl Oncol ; 44: 101945, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38555742

RESUMO

Metformin, as the preferred antihyperglycemic drug for type 2 diabetes, has been found to have a significant effect in inhibiting tumor growth in recent years. However, metformin alone in cancer treatment has the disadvantages of high dose concentrations and few targeted cancer types. Increasing studies have confirmed that metformin can be used in combination with conventional anticancer therapy to obtain more promising clinical benefits, which is expected to be rapidly transformed and applied in clinic. Some combination therapy strategies including metformin combined with chemotherapy, radiotherapy, targeted therapy and immunotherapy have been proven to have more significant antitumor effects and longer survival time than monotherapy. In this review, we summarize the synergistic antitumor effects and mechanisms of metformin in combination with other current conventional anticancer therapies. In addition, we update the research progress and the latest prospect of the metformin-combined application in the cancer treatment. This work could provide more evidence and future direction for the clinical application of metformin in antitumor.

13.
Vaccine ; 42(10): 2608-2620, 2024 Apr 11.
Artigo em Inglês | MEDLINE | ID: mdl-38472066

RESUMO

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.


Assuntos
Quitosana , Nanopartículas Metálicas , Nanopartículas , Vacinas , Viola , Suínos , Animais , Camundongos , Ouro/química , Quitosana/química , Nanopartículas/química , Polissacarídeos , Citocinas , Imunoglobulina G
14.
Phytomedicine ; 127: 155476, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38430586

RESUMO

BACKGROUND: Herpes simplex virus type 1 (HSV-1)-induced herpes simplex encephalitis (HSE) has a high mortality rate in clinically immunocompromised patients, while recovered patients often experience neurological sequelae due to neuroinflammation. Nucleoside drugs and nucleoside analogues such as acyclovir and ganciclovir are mainly used in clinical treatment, and the emergence of resistant viral strains makes the development of new anti-herpesvirus encephalitis drugs urgent. Resveratrol is a multifunctional, plant-derived bioactive compound and its antiviral potential is attracting much attention. PURPOSE: This study aimed to investigate the anti-HSV-1 mechanism of resveratrol in microglial cells and in the HSE mouse model. METHODS: The antiviral effect of resveratrol on HSV-1 infection was investigated by plaque assay, virus titer, immunofluorescence, Western blot and time-of-addition assay. The influence of resveratrol on stimulator of interferon gene (STING)/Nuclear Factor kappa B (NF-κB) signaling pathway-mediated neuroinflammation was examined by Western blot, RT-qPCR and ELISA. The interaction between resveratrol and STING/heat shock protein 90 beta (HSP90ß) was evaluated by molecular modeling, co-immunoprecipitation, and drug affinity responsive target stability assay. The therapeutic effect of resveratrol on HSE was evaluated in the HSE mouse model by analyzing weight loss, neurodegenerative symptoms and histopathological scores. RESULTS: Resveratrol inhibited the early process of HSV-1 infection, and interfered with the STING/NF-κB signaling pathway to attenuate HSV-1-induced neuroinflammation and microglial M1 polarization, independent of its classical target Sirtuin1. Mechanistically, resveratrol completely bound to Glu515 and Lys491 of HSP90ß, thus disrupting the HSP90ß-STING interaction and promoting STING degradation. Resveratrol also significantly alleviated viral encephalitis and neuroinflammation caused by HSV-1 in the HSE mouse model. CONCLUSION: Resveratrol acted as a non-classical HSP90ß inhibitor, binding to the STING-HSP90ß interaction site to promote STING degradation and attenuate HSV-1-induced encephalitis and neuroinflammation. These findings suggest the alternative strategy of targeting HSP90ß and resveratrol-mediated inhibition of HSP90ß as a potential antiviral approach.


Assuntos
Encefalite por Herpes Simples , Herpes Simples , Herpesvirus Humano 1 , Animais , Camundongos , Humanos , Encefalite por Herpes Simples/tratamento farmacológico , Encefalite por Herpes Simples/diagnóstico , Antivirais/farmacologia , Antivirais/uso terapêutico , Resveratrol/farmacologia , Resveratrol/uso terapêutico , NF-kappa B/metabolismo , Doenças Neuroinflamatórias , Herpes Simples/tratamento farmacológico
15.
Epilepsy Res ; 201: 107315, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38364765

RESUMO

PURPOSE: Epilepsy is a debilitating disease that can lead to series of social and psychological issues, impairing the quality of life of people with epilepsy (PWE). This survey aimed to investigate the awareness, attitudes, and first-aid knowledge of epilepsy in university students METHOD: This cross-sectional study was conducted in Henan Province, China between January 1 and April 30, 2022. Students majored in education, medicine, science and engineering from 8 universities attended the study. The survey questionnaire comprised 28 questions covering 4 sections: demographic characteristics, awareness of epilepsy, attitudes toward PWE and knowledge of first aid for seizures. RESULTS: A total of 2376 university students completed the questionnaire. 94.7% heard of epilepsy. In the first aid knowledge section, individual question was correctly answered by at least 50% students, 9.3% students correctly answered all questions. Attitude toward PWE was independently (R2 =0.108, F=73.227, p < 0.001) associated with both awareness of epilepsy (B=0.411, p < 0.001) and first aid knowledge of epilepsy (B=0.047, p = 0.001). Among the three majors, medical students had more positive attitudes toward PWE than students majored in education, science and engineering (p < 0.05). However, medical students performed worse among the groups when answering the first aid knowledge questions. CONCLUSION: This survey showed that university students in Central China had a good awareness of epilepsy. For medical students, improvements are necessary for the awareness of the first aid knowledge for seizure.


Assuntos
Epilepsia , Primeiros Socorros , Humanos , Estudos Transversais , Universidades , Qualidade de Vida , Conhecimentos, Atitudes e Prática em Saúde , Epilepsia/terapia , Epilepsia/psicologia , Convulsões , Estudantes/psicologia , Inquéritos e Questionários , China
16.
Epilepsy Res ; 201: 107333, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38422800

RESUMO

BACKGROUND: This study aimed to construct prediction models for the recognizing of anxiety disorders (AD) in patients with epilepsy (PWEs) by combining clinical features with quantitative electroencephalogram (qEEG) features and using machine learning (ML). METHODS: Nineteen clinical features and 20-min resting-state EEG were collected from 71 PWEs comorbid with AD and another 60 PWEs without AD who met the inclusion-exclusion criteria of this study. The EEG were preprocessed and 684 Phase Locking Value (PLV) and 76 Lempel-Ziv Complexity (LZC) features on four bands were extracted. The Fisher score method was used to rank all the derived features. We constructed four models for recognizing AD in PWEs, whether PWEs based on different combinations of features using eXtreme gradient boosting (XGboost) and evaluated these models using the five-fold cross-validation method. RESULTS: The prediction model constructed by combining the clinical, PLV, and LZC features showed the best performance, with an accuracy of 96.18%, precision of 94.29%, sensitivity of 98.33%, F1-score of 96.06%, and Area Under the Curve (AUC) of 0.96. The Fisher score ranking results displayed that the top ten features were depression, educational attainment, α_P3LZC, α_T6-PzPLV, α_F7LZC, ß_Fp2-O1PLV, θ_T4-CzPLV, θ_F7-PzPLV, α_Fp2LZC, and θ_T4-PzPLV. CONCLUSIONS: The model, constructed by combining the clinical and qEEG features PLV and LZC, efficiently identified the presence of AD comorbidity in PWEs and might have the potential to complement the clinical diagnosis. Our findings suggest that LZC features in the α band and PLV features in Fp2-O1 may be potential biomarkers for diagnosing AD in PWEs.


Assuntos
Ansiedade , Epilepsia , Humanos , Ansiedade/diagnóstico , Ansiedade/epidemiologia , Transtornos de Ansiedade/diagnóstico , Transtornos de Ansiedade/epidemiologia , Comorbidade , Epilepsia/diagnóstico , Epilepsia/epidemiologia , Eletroencefalografia , Aprendizado de Máquina
17.
Food Res Int ; 177: 113918, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38225119

RESUMO

The tailing phenomenon, where the survival curve of bacteria shows a slow tailing period after a rapid decline, is a ubiquitous inactivation kinetics process in the advanced plasma sterilization field. While classical models suggest that bacterial resistance dispersion causes the tailing phenomenon, experiments suggest that the non-uniform spatial distribution of spores (clustered structure) is the cause. However, no existing inactivation kinetics model can accurately describe spatial heterogeneity. In this paper, we propose a lattice model based on percolation theory to explain the inactivation kinetics by considering the non-uniform spatial distribution of spores and plasma. Our model divides spores into non-clustered and clustered types and distinguishes between short-tailing and long-tailing compositions and their formation mechanisms. By systematically studying the effects of different spore and plasma parameters on the tailing phenomenon, we provide a reasonable explanation for the kinetic law of the plasma sterilization survival curve and the mechanism of the tailing phenomenon in various cases. As an example, our model accurately explains the 80-second kinetics of atmospheric pressure plasma inactivation of spores, a process that previous models struggled to understand due to its multi-stage and long-tail phenomena. Our model predicts that increasing the spatial distribution probability of plasma can shorten the complete killing time under the same total energy, and we validate this prediction through experiments. Our model successfully explains the seemingly irregular plasma sterilization survival curve and deepens our understanding of the tailing phenomenon in plasma sterilization. This study offers valuable insights for the sterilization of food surfaces using plasma technology, and could serve as a guide for practical applications.


Assuntos
Gases em Plasma , Esporos Bacterianos , Gases em Plasma/farmacologia , Descontaminação , Esterilização , Esporos
18.
Brain Res ; 1824: 148662, 2024 02 01.
Artigo em Inglês | MEDLINE | ID: mdl-37924926

RESUMO

OBJECTIVE: Anxiety disorders (AD) are critical factors that significantly (about one-fifth) impact the quality of life (QoL) in patients with epilepsy (PWE). Objective diagnostic methods have contributed to the identification of PWE susceptible to AD. This study aimed to identify AD in PWE by constructing a diagnostic model based on the phase locking value (PLV) and Lempel-Ziv Complexity (LZC) features of the electroencephalogram (EEG). METHODS: EEG data from 131 patients with epilepsy (PWE) were enrolled in this study. Patients were divided into two groups, anxiety disorder (AD, n = 61) and non-anxiety disorder (NAD, n = 70), according to the Hamilton Rating Scale for Anxiety (HAM-A). Support vector machine (SVM) and K-Nearest-Neighbor(KNN) algorithms were used to construct three models - the PLVEEG, LZCEEG, and PLVEEG + LZCEEG feature models. Finally, the area under the receiver operating characteristic curve (AUC) and statistical analyses were performed to evaluate the model performance. RESULTS: The efficiency of the KNN-based PLCEEG + LZCEEG feature model was the best, and the accuracy, precision, recall, F1-score, and AUC of the model after five-fold cross-validations scores were 87.89 %, 82.27 %, 98.33 %, 88.95 %, and 0.89, respectively. When the model efficiency was optimal, 29 EEG features were suggested. Further analysis of these features indicated 22 EEG features that were significantly different between the two groups, including 50 % features of the alpha (α)-band. CONCLUSIONS: The PLVEEG + LZCEEG model features can identify AD in PWE. The PLVEEG and LZCEEG characteristics of the α-band may further be explored as potential biomarkers for AD in PWE.


Assuntos
Epilepsia , Qualidade de Vida , Humanos , Epilepsia/diagnóstico , Ansiedade/diagnóstico , Transtornos de Ansiedade , Eletroencefalografia/métodos
19.
Pest Manag Sci ; 80(3): 1446-1453, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-37946692

RESUMO

BACKGROUND: Soil seedbanks have been recognized as one of the crucial components of agricultural ecosystems. However, studies on the shift in structure and biodiversity of soil seedbanks in herbicide-resistant crop systems are limited, and a functional trait perspective of the soil seedbank is often overlooked. RESULTS: A 6 years experiment was conducted to investigate the roles of region, crop system, and weed management strategy on species richness, functional trait diversity, and composition of the weed seedbank. Species richness was different across the interaction of region and crop system, while functional trait diversity only showed difference across regions. Species and functional trait compositions were affected by the interaction of region and crop system. Specifically, the compositional difference among crop systems was mainly determined by the significant heterogeneity of group dispersion. CONCLUSION: Growers and practitioners should consider weed functional traits in developing lasting agricultural management strategies. Long-term weed research should draw attention to the impact of transgenic crop systems and specific management tactics on weed dispersal, functional composition, and resistance evolution of weed species in such agroecosystems. © 2023 The Authors. Pest Management Science published by John Wiley & Sons Ltd on behalf of Society of Chemical Industry.


Assuntos
Herbicidas , Estados Unidos , Herbicidas/farmacologia , Controle de Plantas Daninhas , Banco de Sementes , Plantas Daninhas , Ecossistema , Produtos Agrícolas , Resistência a Herbicidas , Solo
20.
Int J Biol Macromol ; 257(Pt 2): 128670, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38070794

RESUMO

In this study, a novel nano-drug delivery system (CS-Au NPs) based on gold nanoparticles (Au NPs) and chitosan (CS) that modified Myricaria germanica polysaccharide (MGP) was developed to enhance immune responses. At a MGP to CS Au ratio of 5:1, CS-Au-MGP NPs had a loading capacity of 78.27 %. The structure of CS-Au-MGP NPs were characterized by Transmission electron microscope, TEM-energy dispersive spectroscopy mapping, Fourier transform infrared spectroscopy, X-ray photoelectron spectrometer, particle size and zeta-potential distribution analysis. Under weakly acidic conditions, in vitro CS-Au-MGP NPs release was most effective. In vivo showed that co-immunization with CS-Au-MGP NPs and PCV2 significantly increased the organ index of the thymus, spleen, and liver in mice. Additionally, CS-Au-MGP NPs significantly increased the levels of IgG, IgG1, and IgG2a antibodies, as well as IFN-γ and IL-6 levels. Furthermore, the CS-Au-MGP NPs promoted proliferation of spleen T and B lymphocytes, increased the number of CD3+, CD4+, and CD8+ cells, and increased the CD4+/CD8+ T cell ratio. Meanwhile, CS-Au-MGP NPs remarkably TLR2/IRAK4 pathway activation and mRNA levels of cytokines (IFN-γ and IL-6). These results indicated that CS-Au-MGP NPs could enhance the immune activity, and it could be potentially used as an MGP delivery system for the induction of strong immune responses.


Assuntos
Quitosana , Nanopartículas Metálicas , Nanopartículas , Camundongos , Animais , Quitosana/química , Ouro/química , Interleucina-6 , Nanopartículas/química , Polissacarídeos/farmacologia , Imunidade
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