Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 442
Filtrar
1.
Support Care Cancer ; 32(7): 407, 2024 Jun 04.
Artigo em Inglês | MEDLINE | ID: mdl-38833106

RESUMO

OBJECTIVE: Poor adherence to oral chemotherapy adversely impacts clinical outcomes and escalates overall healthcare costs. Despite barriers to medication adherence, a significant gap remains in assessing adherence to oral chemotherapy among multiple myeloma (MM) patients with lower socioeconomic status. Hence, our study aims to evaluate immunomodulator adherence in MM patients at a county hospital, primarily serving underrepresented and indigent individuals with low socioeconomic status across the greater Houston area. METHODS: Inclusion criteria composed of patients diagnosed with MM, aged at least 18 years, and treated with lenalidomide or pomalidomide-two widely used immunomodulators-for a minimum of 2 months or having two or more records of dispensation between May 2019 and May 2021. Adherence was gauged using an adjusted version of the medication possession ratio (MPR). RESULTS: Sixty-two patients were enrolled, yielding a mean MPR value of 88% (SD, ± 18.9). Of these, 43 patients (69.3%) demonstrated adherence with an MPR of ≥ 0.90. A significant difference was found in treatment duration between the adherent (mean 8.8 months; SD, ± 7.2) and non-adherent (mean 13.4 months; SD, ± 7.9) groups (p = 0.027). Notably, race/ethnicity demonstrated a significant difference (p = 0.048), driven by disparities in African American and Hispanic representation across adherence levels. CONCLUSION: In summary, our findings highlight race and treatment duration to be predictors of immunomodulator adherence among MM patients with lower socioeconomic status. Further research is imperative to devise and test innovative interventions aimed at enhancing medication adherence, thereby contributing to improved survival and healthcare quality in this population.


Assuntos
Lenalidomida , Adesão à Medicação , Mieloma Múltiplo , Classe Social , Talidomida , Humanos , Mieloma Múltiplo/tratamento farmacológico , Masculino , Estudos Retrospectivos , Adesão à Medicação/estatística & dados numéricos , Feminino , Pessoa de Meia-Idade , Idoso , Talidomida/uso terapêutico , Talidomida/análogos & derivados , Talidomida/administração & dosagem , Lenalidomida/administração & dosagem , Lenalidomida/uso terapêutico , Fatores Imunológicos/uso terapêutico , Fatores Imunológicos/administração & dosagem , Agentes de Imunomodulação/uso terapêutico , Agentes de Imunomodulação/administração & dosagem , Agentes de Imunomodulação/farmacologia , Texas , Idoso de 80 Anos ou mais , Adulto
3.
Food Res Int ; 189: 114573, 2024 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-38876600

RESUMO

Food proteins and their peptides play a significant role in the important biological processes and physiological functions of the body. The peptides show diverse biological benefits ranging from anticancer to antihypertensive, anti-obesity, and immunomodulatory, among others. In this review, an overview of food protein digestion in the gastrointestinal tract and the mechanisms involved was presented. As some proteins remain resistant and undigested, the multifarious factors (e.g. protein type and structure, microbial composition, pH levels and redox potential, host factors, etc.) affecting their colonic fermentation, the derived peptides, and amino acids that evade intestinal digestion are thus considered. The section that follows focuses on the mechanisms of the peptides with anticancer, antihypertensive, anti-obesity, and immunomodulatory effects. As further considerations were made, it is concluded that clinical studies targeting a clear understanding of the gastrointestinal stability, bioavailability, and safety of food-based peptides are still warranted.


Assuntos
Fármacos Antiobesidade , Anti-Hipertensivos , Antineoplásicos , Proteínas Alimentares , Digestão , Peptídeos , Humanos , Anti-Hipertensivos/farmacologia , Proteínas Alimentares/metabolismo , Peptídeos/farmacologia , Antineoplásicos/farmacologia , Fármacos Antiobesidade/farmacologia , Trato Gastrointestinal/metabolismo , Animais , Fatores Imunológicos/farmacologia , Microbioma Gastrointestinal/efeitos dos fármacos , Disponibilidade Biológica , Agentes de Imunomodulação/farmacologia
4.
Carbohydr Polym ; 339: 122214, 2024 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-38823900

RESUMO

The polysaccharide, RGP2, was isolated from Russula griseocarnosa and its immunostimulatory effects were confirmed in cyclophosphamide (CTX)-induced immunosuppressed mice. Following purification via chromatography, structural analysis revealed that RGP2 had a molecular weight of 11.82 kDa and consisted of glucose (Glc), galactose (Gal), mannose, glucuronic acid and glucosamine. Bond structure analysis and nuclear magnetic resonance characterization confirmed that the main chain of RGP2 was formed by →6)-ß-D-Glcp-(1→, →3)-ß-D-Glcp-(1→ and →6)-α-D-Galp-(1→, which was substituted at O-3 of →6)-ß-D-Glcp-(1→ by ß-D-Glcp-(1→. RGP2 was found to ameliorate pathological damage in the spleen and enhance immune cell activity in immunosuppressed mice. Based on combined multiomics analysis, RGP2 altered the abundance of immune-related microbiota (such as Lactobacillus, Faecalibacterium, and Bacteroides) in the gut and metabolites (uridine, leucine, and tryptophan) in the serum. Compared with immunosuppressed mice, RGP2 also restored the function of antigen-presenting cells, promoted the polarization of macrophages into the M1 phenotype, positively affected the differentiation of helper T cells, and inhibited regulatory T cell differentiation through the protein kinase B (AKT)/mechanistic target of rapamycin (mTOR) pathway, ultimately exerting an immune boosting function. Overall, our findings highlight therapeutic strategies to alleviate CTX-induced immunosuppression in a clinical setting.


Assuntos
Basidiomycota , Diferenciação Celular , Glucanos , Animais , Camundongos , Basidiomycota/química , Glucanos/química , Glucanos/farmacologia , Glucanos/isolamento & purificação , Diferenciação Celular/efeitos dos fármacos , Linfócitos T/efeitos dos fármacos , Agentes de Imunomodulação/farmacologia , Agentes de Imunomodulação/química , Masculino , Fatores Imunológicos/farmacologia , Fatores Imunológicos/química , Fatores Imunológicos/isolamento & purificação , Ciclofosfamida/farmacologia , Camundongos Endogâmicos BALB C , Microbioma Gastrointestinal/efeitos dos fármacos
5.
Carbohydr Polym ; 340: 122259, 2024 Sep 15.
Artigo em Inglês | MEDLINE | ID: mdl-38858019

RESUMO

Our previous investigations have successfully identified the repeating structural units of EPS53, an exopolysaccharide derived from Streptococcus thermophilus XJ53 fermented milk, and substantiated its potential immunomodulatory properties. The present study further elucidated the structural characteristics of EPS53 and investigated the underlying mechanisms governing its in vitro immunoreactivity as well as its in vivo immunoreactivity. The results obtained from multi-detector high performance gel filtration chromatography revealed that EPS53 adopted a rigid rod conformation in aqueous solution, with the weight-average molecular weight of 1464 kDa, the number-average molecular weight of 694 kDa, and the polydispersity index of 2.11. Congo red experiment confirmed the absence of a triple helix conformation. Scanning electron microscopy showed that EPS53 displayed a three-dimensional fibrous structure covered with flakes. The in vitro findings indicated that EPS53 enhanced phagocytosis ability, reactive oxygen species (ROS) production, and cytokine levels of macrophages via the TLR4-mediated NF-κB/MAPK signaling pathways as confirmed by immunofluorescence staining experiments, inhibition blocking experiments, and Western blot assay. Additionally, the in vivo experiments demonstrated that EPS53 significantly increased macrophage and neutrophil number while enhancing NO and ROS levels in zebrafish larvae; thus, providing further evidence for the immunomodulatory efficacy of EPS53.


Assuntos
Fagocitose , Polissacarídeos Bacterianos , Streptococcus thermophilus , Peixe-Zebra , Animais , Polissacarídeos Bacterianos/química , Polissacarídeos Bacterianos/farmacologia , Camundongos , Células RAW 264.7 , Fagocitose/efeitos dos fármacos , Receptor 4 Toll-Like/metabolismo , NF-kappa B/metabolismo , Espécies Reativas de Oxigênio/metabolismo , Macrófagos/efeitos dos fármacos , Macrófagos/metabolismo , Citocinas/metabolismo , Fatores Imunológicos/farmacologia , Fatores Imunológicos/química , Agentes de Imunomodulação/farmacologia , Agentes de Imunomodulação/química , Transdução de Sinais/efeitos dos fármacos
6.
Adv Exp Med Biol ; 1451: 337-354, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38801589

RESUMO

Poxviruses target innate immunity mediators such as tumor necrosis factors, interleukins, interferons, complement, and chemokines. It also targets adaptive immunity such as CD4+ T cells, CD4+ T cells, and B cells. Emerging of the recent epidemic of monkeypox virus (MPXV), a zoonotic disease native to Central and Western Africa, besides the lack of permitted treatments for poxviruses infections, encouraged researchers to identify effective inhibitors to help in preventing and treating poxviruses infections. Natural bioactive components, particularly polyphenolics, are promising for creating powerful antioxidants, anti-inflammatory, immune-stimulating, and antiviral agents. As a result, they are potentially effective therapies for preventing and treating viral diseases, such as infections caused by poxviruses including the recent pandemic MPXV. Polyphenolics: rosmarinic acid, caffeic acid, resveratrol, quercitrin, myricitrin, gingerol, gallotannin, and propolis-benzofuran A, as well as isoquinoline alkaloids: galanthamine and thalimonine represent prospective antiviral agents against MPXV, they can inhibit MPXV and other poxviruses via targeting different viral elements including DNA Topoisomerase I (TOP1), Thymidine Kinase (TK), serine/threonine protein kinase (Ser/Thr kinase), and protein A48R. The bioactive extracts of different traditional plants including Guiera senegalensis, Larrea tridentata, Sarracenia purpurea, Kalanchoe pinnata (Lam.) Pers., Zingiber officinale Roscoe, Quercus infectoria, Rhus chinensis, Prunella vulgaris L., Salvia rosmarinus, and Origanum vulgare also can inhibit the growth of different poxviruses including MPXV, vaccinia virus (VACV), variola virus, buffalopox virus, fowlpox virus, and cowpox virus. There is an urgent need for additional molecular studies to identify and confirm the anti-poxviruses properties of various natural bioactive components, especially those that showed potent antiviral activity against other viruses.


Assuntos
Antivirais , Infecções por Poxviridae , Poxviridae , Humanos , Infecções por Poxviridae/tratamento farmacológico , Infecções por Poxviridae/virologia , Infecções por Poxviridae/imunologia , Animais , Antivirais/farmacologia , Antivirais/uso terapêutico , Antivirais/química , Poxviridae/efeitos dos fármacos , Agentes de Imunomodulação/farmacologia , Agentes de Imunomodulação/uso terapêutico , Agentes de Imunomodulação/química , Terapias Complementares/métodos , Produtos Biológicos/farmacologia , Produtos Biológicos/uso terapêutico , Produtos Biológicos/química
7.
Int J Biol Macromol ; 270(Pt 2): 132222, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38729468

RESUMO

Fungal polysaccharides have been explored by many for both structural studies and biological activities, but few studies have been done on the extracellular polysaccharides of Dictyophora rubrovalvata, so a new exopolysaccharide was isolated from Dictyophora rubrovalvata and its structure and its immunological activity were investigated. The crude exopolysaccharide (EPS) was purified by DEAE52 cellulose and Sephadex G-200 to obtain a new acidic polysaccharide (DR-EPS). DR-EPS (2.66 × 103 kDa) was consisted mainly of mannose, glucose, galactose and glucuronic acid with a molar ratio of 1: 0.86: 0.20: 0.01. In addition, DR-EPS increased the phagocytic activity of RAW264.7 cells up to 2.67 times of the blank control group. DR-EPS improved intracellular nucleic acid and glycogen metabolism as observed by AO and PAS staining. DR-EPS(40 µg/mL) promoted NO production up to 30.66 µmol, enhanced acid phosphatase (ACP) and superoxide dismutase (SOD) activities, with activity maxima of 660 U/gprot and 96.27 U/mgprot, respectively, and DR-EPS (160 µg / mL) significantly increased the lysozyme content as 2.73 times of the control group. The good immunological activity of extracellular polysaccharides of Dictyophora rubrovalvata provides directions for the use of fermentation broths.


Assuntos
Polissacarídeos Fúngicos , Camundongos , Animais , Células RAW 264.7 , Polissacarídeos Fúngicos/farmacologia , Polissacarídeos Fúngicos/química , Polissacarídeos Fúngicos/isolamento & purificação , Óxido Nítrico/metabolismo , Fatores Imunológicos/farmacologia , Fatores Imunológicos/química , Fatores Imunológicos/isolamento & purificação , Fagocitose/efeitos dos fármacos , Agentes de Imunomodulação/farmacologia , Agentes de Imunomodulação/química , Agentes de Imunomodulação/isolamento & purificação , Superóxido Dismutase/metabolismo , Macrófagos/efeitos dos fármacos , Macrófagos/metabolismo , Macrófagos/imunologia , Fosfatase Ácida/metabolismo
8.
Molecules ; 29(9)2024 Apr 26.
Artigo em Inglês | MEDLINE | ID: mdl-38731500

RESUMO

A robust, well-functioning immune system is the cornerstone of good health. Various factors may influence the immune system's effectiveness, potentially leading to immune system failure. This review aims to provide an overview of the structure and action of immunomodulators isolated from African medicinal plants. The research was conducted according to PRISMA guidelines. Full-text access research articles published in English up to December 2023, including plant characteristics, isolated phytochemicals, and immuno-modulatory activities, were screened. The chemical structures of the isolated compounds were generated using ChemDraw® (version 12.0.1076), and convergent and distinctive signaling pathways were highlighted. These phytochemicals with demonstrated immunostimulatory activity include alkaloids (berberine, piperine, magnoflorine), polysaccharides (pectin, glucan, acemannan, CALB-4, GMP90-1), glycosides (syringin, cordifolioside, tinocordiside, aucubin), phenolic compounds (ferulic acid, vanillic acid, eupalitin), flavonoids (curcumin, centaurein, kaempferin, luteolin, guajaverin, etc.), terpenoids (oleanolic acid, ursolic acid, betulinic acid, boswellic acids, corosolic acid, nimbidin, andrographolides). These discussed compounds exert their effects through various mechanisms, targeting the modulation of MAPKs, PI3K-Akt, and NF-kB. These mechanisms can support the traditional use of medicinal plants to treat immune-related diseases. The outcomes of this overview are to provoke structural action optimization, to orient research on particular natural chemicals for managing inflammatory, infectious diseases and cancers, or to boost vaccine immunogenicity.


Assuntos
Compostos Fitoquímicos , Plantas Medicinais , Plantas Medicinais/química , Compostos Fitoquímicos/farmacologia , Compostos Fitoquímicos/química , Humanos , Extratos Vegetais/química , Extratos Vegetais/farmacologia , Agentes de Imunomodulação/farmacologia , Agentes de Imunomodulação/química , Agentes de Imunomodulação/isolamento & purificação , Fatores Imunológicos/farmacologia , Fatores Imunológicos/química , Fatores Imunológicos/isolamento & purificação , África , Animais
9.
Int J Mol Sci ; 25(10)2024 May 09.
Artigo em Inglês | MEDLINE | ID: mdl-38791191

RESUMO

Cancer immunotherapy relies on the insight that the immune system can be used to defend against malignant cells. The aim of cancer immunotherapy is to utilize, modulate, activate, and train the immune system to amplify antitumor T-cell immunity. In parallel, the immune system response to damaged tissue is also crucial in determining the success or failure of an implant. Due to their extracellular matrix mimetics and tunable chemical or physical performance, hydrogels are promising platforms for building immunomodulatory microenvironments for realizing cancer therapy and tissue regeneration. However, submicron or nanosized pore structures within hydrogels are not favorable for modulating immune cell function, such as cell invasion, migration, and immunophenotype. In contrast, hydrogels with a porous structure not only allow for nutrient transportation and metabolite discharge but also offer more space for realizing cell function. In this review, the design strategies and influencing factors of porous hydrogels for cancer therapy and tissue regeneration are first discussed. Second, the immunomodulatory effects and therapeutic outcomes of different porous hydrogels for cancer immunotherapy and tissue regeneration are highlighted. Beyond that, this review highlights the effects of pore size on immune function and potential signal transduction. Finally, the remaining challenges and perspectives of immunomodulatory porous hydrogels are discussed.


Assuntos
Hidrogéis , Neoplasias , Hidrogéis/química , Humanos , Porosidade , Animais , Neoplasias/terapia , Neoplasias/imunologia , Imunoterapia/métodos , Imunomodulação/efeitos dos fármacos , Engenharia Tecidual/métodos , Agentes de Imunomodulação/química , Agentes de Imunomodulação/farmacologia , Agentes de Imunomodulação/uso terapêutico , Microambiente Tumoral/imunologia
10.
Int J Mol Sci ; 25(10)2024 May 14.
Artigo em Inglês | MEDLINE | ID: mdl-38791372

RESUMO

Mulberry is a rapidly growing plant that thrives in diverse climatic, topographical, and soil types, spanning temperature and temperate countries. Mulberry plants are valued as functional foods for their abundant chemical composition, serving as a significant reservoir of bioactive compounds like proteins, polysaccharides, phenolics, and flavonoids. Moreover, these compounds displayed potent antioxidant activity by scavenging free radicals, inhibiting reactive oxygen species generation, and restoring elevated nitric oxide production induced by LPS stimulation through the downregulation of inducible NO synthase expression. Active components like oxyresveratrol found in Morus demonstrated anti-inflammatory effects by inhibiting leukocyte migration through the MEK/ERK signaling pathway. Gallic and chlorogenic acids in mulberry leaves (ML) powder-modulated TNF, IL-6, and IRS1 proteins, improving various inflammatory conditions by immune system modulation. As we delve deeper into understanding its anti-inflammatory potential and how it works therapeutically, it is crucial to refine the extraction process to enhance the effectiveness of its bioactive elements. Recent advancements in extraction techniques, such as solid-liquid extraction, pressurized liquid extraction, superficial fluid extraction, microwave-assisted extraction, and ultrasonic-assisted extraction, are being explored. Among the extraction methods tested, including Soxhlet extraction, maceration, and ultrasound-assisted extraction (UAE), UAE demonstrated superior efficiency in extracting bioactive compounds from mulberry leaves. Overall, this comprehensive review sheds light on the potential of mulberry as a natural immunomodulatory agent and provides insights into its mechanisms of action for future research and therapeutic applications.


Assuntos
Morus , Extratos Vegetais , Morus/química , Extratos Vegetais/farmacologia , Extratos Vegetais/química , Humanos , Animais , Anti-Inflamatórios/farmacologia , Anti-Inflamatórios/química , Agentes de Imunomodulação/farmacologia , Agentes de Imunomodulação/química , Fatores Imunológicos/farmacologia , Fatores Imunológicos/química , Folhas de Planta/química
11.
Int J Mol Sci ; 25(10)2024 May 15.
Artigo em Inglês | MEDLINE | ID: mdl-38791439

RESUMO

Lefamulin is a first-in-class systemic pleuromutilin antimicrobial and potent inhibitor of bacterial translation, and the most recent novel antimicrobial approved for the treatment of community-acquired pneumonia (CAP). It exhibits potent antibacterial activity against the most prevalent bacterial pathogens that cause typical and atypical pneumonia and other infectious diseases. Early studies indicate additional anti-inflammatory activity. In this study, we further investigated the immune-modulatory activity of lefamulin in the influenza A/H1N1 acute respiratory distress syndrome (ARDS) model in BALB/c mice. Comparators included azithromycin, an anti-inflammatory antimicrobial, and the antiviral oseltamivir. Lefamulin significantly decreased the total immune cell infiltration, specifically the neutrophils, inflammatory monocytes, CD4+ and CD8+ T-cells, NK cells, and B-cells into the lung by Day 6 at both doses tested compared to the untreated vehicle control group (placebo), whereas azithromycin and oseltamivir did not significantly affect the total immune cell counts at the tested dosing regimens. Bronchioalveolar lavage fluid concentrations of pro-inflammatory cytokines and chemokines including TNF-α, IL-6, IL-12p70, IL-17A, IFN-γ, and GM-CSF were significantly reduced, and MCP-1 concentrations were lowered (not significantly) by lefamulin at the clinically relevant 'low' dose on Day 3 when the viral load peaked. Similar effects were also observed for oseltamivir and azithromycin. Lefamulin also decreased the viral load (TCID50) by half a log10 by Day 6 and showed positive effects on the gross lung pathology and survival. Oseltamivir and lefamulin were efficacious in the suppression of the development of influenza-induced bronchi-interstitial pneumonia, whereas azithromycin did not show reduced pathology at the tested treatment regimen. The observed anti-inflammatory and immune-modulatory activity of lefamulin at the tested treatment regimens highlights a promising secondary pharmacological property of lefamulin. While these results require confirmation in a clinical trial, they indicate that lefamulin may provide an immune-modulatory activity beyond its proven potent antibacterial activity. This additional activity may benefit CAP patients and potentially prevent acute lung injury (ALI) and ARDS.


Assuntos
Modelos Animais de Doenças , Diterpenos , Vírus da Influenza A Subtipo H1N1 , Camundongos Endogâmicos BALB C , Infecções por Orthomyxoviridae , Animais , Vírus da Influenza A Subtipo H1N1/efeitos dos fármacos , Camundongos , Infecções por Orthomyxoviridae/tratamento farmacológico , Infecções por Orthomyxoviridae/imunologia , Infecções por Orthomyxoviridae/virologia , Diterpenos/farmacologia , Diterpenos/uso terapêutico , Citocinas/metabolismo , Azitromicina/farmacologia , Azitromicina/uso terapêutico , Oseltamivir/farmacologia , Oseltamivir/uso terapêutico , Feminino , Pulmão/imunologia , Pulmão/virologia , Pulmão/efeitos dos fármacos , Pulmão/patologia , Antivirais/farmacologia , Antivirais/uso terapêutico , Tetra-Hidronaftalenos/farmacologia , Tetra-Hidronaftalenos/uso terapêutico , Síndrome do Desconforto Respiratório/tratamento farmacológico , Síndrome do Desconforto Respiratório/imunologia , Síndrome do Desconforto Respiratório/virologia , Agentes de Imunomodulação/farmacologia , Agentes de Imunomodulação/uso terapêutico , Líquido da Lavagem Broncoalveolar/imunologia , Compostos Policíclicos , Tioglicolatos
12.
Neurology ; 102(10): e209297, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38696733

RESUMO

BACKGROUND AND OBJECTIVES: Among infectious etiologies of encephalitis, herpes simplex virus type 1 (HSV-1) is most common, accounting for ∼15%-40% of adult encephalitis diagnoses. We aim to investigate the association between immune status and HSV encephalitis (HSVE). Using a US Medicaid database of 75.6 million persons, we evaluated the association between HSVE and autoimmune conditions, exposure to immunosuppressive and immunomodulatory medications, and other medical comorbidities. METHODS: We used the US Medicaid Analytic eXtract data between 2007 and 2010 from the 29 most populated American states. We first examined the crude incidence of HSVE in the population. We then age and sex-matched adult cases of HSVE with a sufficient enrollment period (12 months before HSVE diagnosis) to a larger control population without HSVE. In a case-control analysis, we examined the association between HSVE and exposure to both autoimmune disease and immunosuppressive/immunomodulatory medications. Analyses were conducted with conditional logistic regression progressively adjusting for sociodemographic factors, Charlson Comorbidity Index, and non-autoimmune comorbidities. RESULTS: Incidence of HSVE was ∼3.01 per 105 person-years among adults. A total of 951 HSVE cases and 95,100 age and sex-matched controls were compared. The HSVE population had higher rates of medical comorbidities than the control population. The association of HSVE and autoimmune conditions was strong (adjusted odds ratio (OR) 2.6; 95% CI 2.2-3.2). The association of HSVE and immunomodulating medications had an OR of 2.2 (CI 1.9-2.6), also after covariate adjustment. When both exposures were included in regression models, the associations remained robust: OR 2.3 (CI 1.9-2.7) for autoimmune disease and 2.0 (CI 1.7-2.3) for immunosuppressive and immunomodulatory medications. DISCUSSION: In a large, national population, HSVE is strongly associated with preexisting autoimmune disease and exposure to immunosuppressive and immunomodulatory medications. The role of antecedent immune-related dysregulation may have been underestimated to date.


Assuntos
Doenças Autoimunes , Encefalite por Herpes Simples , Agentes de Imunomodulação , Humanos , Feminino , Masculino , Encefalite por Herpes Simples/epidemiologia , Encefalite por Herpes Simples/imunologia , Doenças Autoimunes/epidemiologia , Doenças Autoimunes/imunologia , Adulto , Pessoa de Meia-Idade , Estados Unidos/epidemiologia , Agentes de Imunomodulação/uso terapêutico , Agentes de Imunomodulação/efeitos adversos , Estudos de Casos e Controles , Incidência , Imunossupressores/efeitos adversos , Imunossupressores/uso terapêutico , Adulto Jovem , Medicaid , Idoso , Adolescente , Comorbidade
13.
Front Immunol ; 15: 1374541, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38807598

RESUMO

Objective: The coronavirus disease 2019 (COVID-19) spread rapidly and claimed millions of lives worldwide. Acute respiratory distress syndrome (ARDS) is the major cause of COVID-19-associated deaths. Due to the limitations of current drugs, developing effective therapeutic options that can be used rapidly and safely in clinics for treating severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infections is necessary. This study aims to investigate the effects of two food-extracted immunomodulatory agents, ajoene-enriched garlic extract (AGE) and cruciferous vegetables-extracted sulforaphane (SFN), on anti-inflammatory and immune responses in a SARS-CoV-2 acute lung injury mouse model. Methods: In this study, we established a mouse model to mimic the SARS-CoV-2 infection acute lung injury model via intratracheal injection of polyinosinic:polycytidylic acid (poly[I:C]) and SARS-CoV-2 recombinant spike protein (SP). After the different agents treatment, lung sections, bronchoalveolar lavage fluid (BALF) and fresh faeces were harvested. Then, H&E staining was used to examine symptoms of interstitial pneumonia. Flow cytometry was used to examine the change of immune cell populations. Multiplex cytokines assay was used to examine the inflammatory cytokines.16S rDNA high-throughput sequencing was used to examine the change of gut microbiome. Results: Our results showed that AGE and SFN significantly suppressed the symptoms of interstitial pneumonia, effectively inhibited the production of inflammatory cytokines, decreased the percentage of inflammatory cell populations, and elevated T cell populations in the mouse model. Furthermore, we also observed that the gut microbiome of genus Paramuribaculum were enriched in the AGE-treated group. Conclusion: Here, for the first time, we observed that these two novel, safe, and relatively inexpensive immunomodulatory agents exhibited the same effects on anti-inflammatory and immune responses as neutralizing monoclonal antibodies (mAbs) against interleukin 6 receptor (IL-6R), which have been suggested for treating COVID-19 patients. Our results revealed the therapeutic ability of these two immunomodulatory agents in a mouse model of SARS-CoV-2 acute lung injury by promoting anti-inflammatory and immune responses. These results suggest that AGE and SFN are promising candidates for the COVID-19 treatment.


Assuntos
Lesão Pulmonar Aguda , Enzima de Conversão de Angiotensina 2 , Anti-Inflamatórios , Tratamento Farmacológico da COVID-19 , COVID-19 , Modelos Animais de Doenças , Agentes de Imunomodulação , SARS-CoV-2 , Animais , Camundongos , Lesão Pulmonar Aguda/imunologia , Lesão Pulmonar Aguda/tratamento farmacológico , Lesão Pulmonar Aguda/etiologia , COVID-19/imunologia , SARS-CoV-2/imunologia , Agentes de Imunomodulação/farmacologia , Agentes de Imunomodulação/uso terapêutico , Anti-Inflamatórios/uso terapêutico , Anti-Inflamatórios/farmacologia , Enzima de Conversão de Angiotensina 2/metabolismo , Enzima de Conversão de Angiotensina 2/genética , Isotiocianatos/farmacologia , Isotiocianatos/uso terapêutico , Sulfóxidos , Humanos , Citocinas/metabolismo , Glicoproteína da Espícula de Coronavírus/imunologia , Pulmão/imunologia , Pulmão/patologia , Pulmão/virologia , Pulmão/efeitos dos fármacos , Masculino , Poli I-C , Extratos Vegetais/farmacologia , Extratos Vegetais/uso terapêutico
14.
PLoS One ; 19(5): e0304713, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38820477

RESUMO

Argentatins are secondary metabolites synthesized by guayule (Parthenium argentatum A. Gray) with numerous potential medical applications. In addition to inhibiting insect growth, they are endowed with several pharmacological properties including antimicrobial and antitumorigenic activity. However, their potential as immunomodulators remains unexplored. The aim of the present study was to investigate whether argentatins can modulate the function of the immune system. Human mesenchymal stem cells were treated with argentatins and the production of several anti- and proinflammatory cytokines was evaluated. The effect of argentatins on the polarization of CD4+ T-lymphocytes and macrophages was also assessed. Results demonstrated that argentatins can modulate the production of proinflammatory cytokines and the polarization of cellular phenotypes, including Th2 lymphocytes and M1 macrophages. These findings suggest that argentatins are promising therapeutic agents in autoimmune or allergic diseases, and open new perspectives for the investigation of argentatins in immune response and in the development of more targeted and effective immunomodulatory therapies.


Assuntos
Citocinas , Humanos , Citocinas/metabolismo , Células-Tronco Mesenquimais/imunologia , Células-Tronco Mesenquimais/efeitos dos fármacos , Células-Tronco Mesenquimais/metabolismo , Macrófagos/imunologia , Macrófagos/efeitos dos fármacos , Macrófagos/metabolismo , Fatores Imunológicos/farmacologia , Agentes de Imunomodulação/farmacologia , Linfócitos T CD4-Positivos/imunologia , Linfócitos T CD4-Positivos/efeitos dos fármacos
15.
Pharmacol Res ; 204: 107203, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38719196

RESUMO

Recent research has demonstrated the immunomodulatory potential of Panax notoginseng in the treatment of chronic inflammatory diseases and cerebral hemorrhage, suggesting its significance in clinical practice. Nevertheless, the complex immune activity of various components has hindered a comprehensive understanding of the immune-regulating properties of Panax notoginseng, impeding its broader utilization. This review evaluates the effect of Panax notoginseng to various types of white blood cells, elucidates the underlying mechanisms, and compares the immunomodulatory effects of different Panax notoginseng active fractions, aiming to provide the theory basis for future immunomodulatory investigation.


Assuntos
Panax notoginseng , Panax notoginseng/química , Humanos , Animais , Sistema Imunitário/efeitos dos fármacos , Leucócitos/efeitos dos fármacos , Leucócitos/imunologia , Agentes de Imunomodulação/farmacologia , Agentes de Imunomodulação/uso terapêutico , Medicamentos de Ervas Chinesas/uso terapêutico , Medicamentos de Ervas Chinesas/farmacologia
16.
ACS Appl Mater Interfaces ; 16(20): 25757-25772, 2024 May 22.
Artigo em Inglês | MEDLINE | ID: mdl-38738757

RESUMO

The development of therapeutics with high antimicrobial activity and immunomodulatory effects is urgently needed for the treatment of infected wounds due to the increasing danger posed by recalcitrant-infected wounds. In this study, we developed light-controlled antibacterial, photothermal, and immunomodulatory biomimetic N/hPDA@M nanoparticles (NPs). This nanoplatform was developed by loading flavonoid naringenin onto hollow mesoporous polydopamine NPs in a π-π-stacked configuration and encasing them with macrophage membranes. First, our N/hPDA@M NPs efficiently neutralized inflammatory factors present within the wound microenvironment by the integration of macrophage membranes. Afterward, the N/hPDA@M NPs effectively dismantled bacterial biofilms through a combination of the photothermal properties of PDA and the quorum sensing inhibitory effects of naringenin. It is worth noting that N/hPDA@M NPs near-infrared-enhanced release of naringenin exhibited specificity toward the NF-κB-signaling pathway, effectively mitigating the inflammatory response. This innovative design not only conferred remarkable antibacterial properties upon the N/hPDA@M NPs but also endowed them with the capacity to modulate inflammatory responses, curbing excessive inflammation and steering macrophage polarization toward the M2 phenotype. As a result, this multifaceted approach significantly contributes to expediting the healing process of infected skin wounds.


Assuntos
Antibacterianos , Biofilmes , Indóis , NF-kappa B , Nanopartículas , Percepção de Quorum , Cicatrização , Biofilmes/efeitos dos fármacos , Nanopartículas/química , Camundongos , NF-kappa B/metabolismo , Antibacterianos/química , Antibacterianos/farmacologia , Cicatrização/efeitos dos fármacos , Animais , Percepção de Quorum/efeitos dos fármacos , Indóis/química , Indóis/farmacologia , Transdução de Sinais/efeitos dos fármacos , Flavanonas/química , Flavanonas/farmacologia , Células RAW 264.7 , Staphylococcus aureus/efeitos dos fármacos , Staphylococcus aureus/fisiologia , Polímeros/química , Polímeros/farmacologia , Macrófagos/efeitos dos fármacos , Macrófagos/metabolismo , Infecção dos Ferimentos/tratamento farmacológico , Infecção dos Ferimentos/microbiologia , Infecção dos Ferimentos/patologia , Agentes de Imunomodulação/química , Agentes de Imunomodulação/farmacologia , Humanos
17.
Cancer Med ; 13(10): e7287, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38770637

RESUMO

Although the development of immunotherapies has been revolutionary in the treatment of several cancers, many cancer types remain unresponsive to immune-based treatment and are largely managed by chemotherapy drugs. However, chemotherapeutics are not infallible and are frequently rendered ineffective as resistance develops from prolonged exposure. Recent investigations have indicated that some chemotherapy drugs have additional functions beyond their normative cytotoxic capacity and are in fact immune-modifying agents. Of the pharmaceuticals with identified immune-editing properties, gemcitabine is well-studied and of interest to clinicians and scientists alike. Gemcitabine is a chemotherapy drug approved for the treatment of multiple cancers, including breast, lung, pancreatic, and ovarian. Because of its broad applications, relatively low toxicity profile, and history as a favorable combinatory partner, there is promise in the recharacterization of gemcitabine in the context of the immune system. Such efforts may allow the identification of suitable immunotherapeutic combinations, wherein gemcitabine can be used as a priming agent to improve immunotherapy efficacy in traditionally insensitive cancers. This review looks to highlight documented immunomodulatory abilities of one of the most well-known chemotherapy agents, gemcitabine, relating to its influence on cells and proteins of the immune system.


Assuntos
Antimetabólitos Antineoplásicos , Gencitabina , Agentes de Imunomodulação , Neoplasias , Animais , Humanos , Antimetabólitos Antineoplásicos/uso terapêutico , Antimetabólitos Antineoplásicos/farmacologia , Gencitabina/farmacologia , Gencitabina/uso terapêutico , Agentes de Imunomodulação/uso terapêutico , Agentes de Imunomodulação/farmacologia , Imunomodulação/efeitos dos fármacos , Imunoterapia/métodos , Neoplasias/tratamento farmacológico , Neoplasias/imunologia
18.
Int Immunopharmacol ; 135: 112251, 2024 Jun 30.
Artigo em Inglês | MEDLINE | ID: mdl-38781608

RESUMO

Nowadays, Nanoparticle-based immunotherapeutic research has invoked global interest due to their unique properties. The immune system is a shielding structure that defends living things from external threats. Before the use of any materials in drug design, it is essential to study the immunological response to avoid triggering undesirable immune responses in the body. This review tries to summarize the properties, various applications, and immunotherapeutic aspects of NP-induced immunomodulation relating to therapeutic development and toxicity in human health. The role of NPs in the immune system and their modulatory functions, resulting in immunosuppression or immunostimulation, exerts benefits or dangers depending on their compositions, sizes, surface chemistry, and so forth. After NPs enter into the body, they can interact with body fluid exposing, them to different body proteins to form protein corona particles and other bio-molecules (DNA, RNA, sugars, etc.), which may alter their bioactivity. Phagocytes are the first immune cells that can interact with foreign materials including nanoparticles. Immunostimulation and immunosuppression operate in two distinct manners. Overall, functionalized nanocarriers optimized various therapeutic implications by stimulating the host immune system and regulating the tranquility of the host immune system. Among others, toxicity and bio-clearance of nanomaterials are always prime concerns at the preclinical and clinical stages before final approval. The interaction of nanoparticles with immune cells causes direct cell damage via apoptosis and necroses as well as immune signaling pathways also become influenced.


Assuntos
Imunomodulação , Nanopartículas , Humanos , Nanopartículas/química , Animais , Imunoterapia/métodos , Agentes de Imunomodulação/farmacologia , Agentes de Imunomodulação/química , Agentes de Imunomodulação/uso terapêutico , Sistema Imunitário/efeitos dos fármacos
19.
Int J Biol Macromol ; 270(Pt 2): 132497, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38763236

RESUMO

To alleviate the adverse effects of chemotherapy and bolster immune function, a novel polysaccharide derived from Sargassum fusiforme named as SFP-αII. The structural composition of SFP-αII predominantly consisted of guluronic and mannuronic acids in a molar ratio of 33.8:66.2, with an average molecular weight of 16.5 kDa. Its structure was primarily characterized by →4)-α-GulA-(1 â†’ and →4)-ß-ManA-(1 â†’ linkages confirmed by FT-IR, methylation, and NMR analyses. The absence of a triple-helix structure was in SFP-αII was confirmed using circular dichroism and Congo red dye assays. The dimensions varied with lengths ranging from 20 nm up to 3 µm revealed by atomic force microscopy (AFM). SFP-αII has been found to enhance immunomodulatory activity in cyclophosphamide (CTX)-induced immunosuppressed mice. This was evidenced by improvements in immune organ indices, cytokine levels, and the release of nitric oxide (NO). Specifically, SFP-αII mitigated immunosuppression by upregulating the secretion of IL-1ß (167.3 %) and TNF-α (227.1 %) at a dose of 400 mg/kg, compared with the CTX group in macrophages. Ultimately, SFP-αII may serve as a mechanism for immune enhancement through modulation of TLR4-mediated NF-κB and MAPK signaling pathways. This integration of traditional Chinese and Western medicine, leveraging SFP-αII as a potential functional food could be pivotal in alleviating immunosuppressive side effects in CTX treatment.


Assuntos
Polissacarídeos , Sargassum , Sargassum/química , Animais , Camundongos , Polissacarídeos/farmacologia , Polissacarídeos/química , Polissacarídeos/isolamento & purificação , Citocinas/metabolismo , Células RAW 264.7 , Ciclofosfamida/farmacologia , Fatores Imunológicos/farmacologia , Fatores Imunológicos/química , Masculino , NF-kappa B/metabolismo , Óxido Nítrico/metabolismo , Peso Molecular , Agentes de Imunomodulação/farmacologia , Agentes de Imunomodulação/química , Algas Comestíveis
20.
Molecules ; 29(9)2024 Apr 30.
Artigo em Inglês | MEDLINE | ID: mdl-38731567

RESUMO

A neutral Polygonatum cyrtonema polysaccharide (NPCP) was isolated and purified from Polygonatum cyrtonema by various chromatographic techniques, including DEAE-52 and Sephadex-G100 chromatography. The structure of NPCP was characterized by HPLC, HPGPC, GC-MS, FT-IR, NMR, and SEM. Results showed that NPCP is composed of glucose (55.4%) and galactose (44.6%) with a molecular weight of 3.2 kDa, and the sugar chain of NPCP was →1)-α-D-Glc-(4→1)-ß-D-Gal-(3→. In vitro bioactivity experiments demonstrated that NPCP significantly enhanced macrophages proliferation and phagocytosis while inhibiting the M1 polarization induced by LPS as well as the M2 polarization induced by IL-4 and IL-13 in macrophages. Additionally, NPCP suppressed the secretion of IL-6 and TNF-α in both M1 and M2 cells but promoted the secretion of IL-10. These results suggest that NPCP could serve as an immunomodulatory agent with potential applications in anti-inflammatory therapy.


Assuntos
Macrófagos , Fagocitose , Polygonatum , Polissacarídeos , Macrófagos/efeitos dos fármacos , Macrófagos/metabolismo , Macrófagos/imunologia , Polygonatum/química , Camundongos , Polissacarídeos/farmacologia , Polissacarídeos/química , Polissacarídeos/isolamento & purificação , Animais , Fagocitose/efeitos dos fármacos , Fatores Imunológicos/farmacologia , Fatores Imunológicos/química , Fatores Imunológicos/isolamento & purificação , Células RAW 264.7 , Citocinas/metabolismo , Proliferação de Células/efeitos dos fármacos , Agentes de Imunomodulação/farmacologia , Agentes de Imunomodulação/química , Agentes de Imunomodulação/isolamento & purificação , Peso Molecular
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA
...