RESUMEN
As a special traditional Chinese medicine, Astragalus polysaccharides for injection (APS, batch no. Zhunzi Z20040086) includes complex polysaccharide macromolecules that may increase the risk upon application. Although fingerprints for quality control are available, the specific active ingredients are unclear. Identifying the active components is the key to reduce the risk of adverse reactions of the drug. In this work, APS was mainly separated into two components, namely, macromolecular component (APS-I) and small molecular components (APS-II). The molecular weight measurement revealed that the average molecular weight of APS-I exceeded 500 kDa, and that of APS-II was 10 kDa. Monosaccharide-composition analysis revealed that APS-I consisted of glucose, galactose, arabinose, rhamnose, and galacturonic acid, with a ratio of approximately 1.5:1:5.4:0.08:0.1. Meanwhile, APS-II consisted of glucose, galactose, arabinose, rhamnose, and galacturonic acid, with a molar ratio of 9:1:1.4:0.04:0.001. Methylation, FT-IR, and NMR analysis indicated that the APS-I monosaccharide residue was linked as follows: D-Glcp-(1â, â4)-D-Glcp-(1â, â2)-L-Rhap-(1â, D-Araf-(1â, â5)-D-Araf-(1â, â2,5)-D-Araf-(1â, â4)-D-Galp-(1 â . Meanwhile, the APS-II monosaccharide residue was connected as follows: α-D-Glcp-(1â, â4)-α-D-Glcp-(1â, â6)-α-D-Glcp-(1â, â4,6)-α-D-Glcp-(1â, â3,4,6)-α-D-Glcp-(1â, â2)-α-L-Rhap-(1â, α-D-Araf-(1â, â5)-α-D-Araf-(1â, â4)-ß-D-Galp-(1 â . Screening experiments on their in vitro immunological activity showed that APS-II had stronger effect on innate and adaptive immunities than APS-I. In vivo animal experiments showed that APS-II can increase the leukocyte level of cyclophosphamide immunosuppressed mice and improve their immunomodulatory ability. Therefore, APS-II is the main active ingredient of APS and is expected to become a new generation of APS products.
Asunto(s)
Planta del Astrágalo , Medicamentos Herbarios Chinos , Monosacáridos , Animales , Proliferación Celular/efectos de los fármacos , Supervivencia Celular/efectos de los fármacos , Cromatografía Líquida de Alta Presión , Medicamentos Herbarios Chinos/análisis , Medicamentos Herbarios Chinos/química , Medicamentos Herbarios Chinos/farmacología , Femenino , Factores Inmunológicos/análisis , Factores Inmunológicos/química , Factores Inmunológicos/farmacología , Espectroscopía de Resonancia Magnética , Ratones , Ratones Endogámicos BALB C , Peso Molecular , Monosacáridos/análisis , Monosacáridos/química , Monosacáridos/farmacología , Fagocitosis/efectos de los fármacos , Células RAW 264.7RESUMEN
Hemorrhagic fevers (HF) resulting from pathogenic arenaviral infections have traditionally been neglected as tropical diseases primarily affecting African and South American regions. There are currently no FDA-approved vaccines for arenaviruses, and treatments have been limited to supportive therapy and use of non-specific nucleoside analogs, such as Ribavirin. Outbreaks of arenaviral infections have been limited to certain geographic areas that are endemic but known cases of exportation of arenaviruses from endemic regions and socioeconomic challenges for local control of rodent reservoirs raise serious concerns about the potential for larger outbreaks in the future. This review synthesizes current knowledge about arenaviral evolution, ecology, transmission patterns, life cycle, modulation of host immunity, disease pathogenesis, as well as discusses recent development of preventative and therapeutic pursuits against this group of deadly viral pathogens.
Asunto(s)
Infecciones por Arenaviridae , Arenavirus/inmunología , Brotes de Enfermedades , Fiebres Hemorrágicas Virales , Tolerancia Inmunológica , Ribavirina/uso terapéutico , África/epidemiología , Infecciones por Arenaviridae/tratamiento farmacológico , Infecciones por Arenaviridae/epidemiología , Infecciones por Arenaviridae/inmunología , Fiebres Hemorrágicas Virales/tratamiento farmacológico , Fiebres Hemorrágicas Virales/epidemiología , Fiebres Hemorrágicas Virales/inmunología , Humanos , América del Sur/epidemiologíaRESUMEN
Millions of children are exposed to concentrations of air pollutants, including fine particulate matter (PM2.5), above safety standards. In the Mexico City Metropolitan Area (MCMA) megacity, children show an early brain imbalance in oxidative stress, inflammation, innate and adaptive immune response-associated genes, and blood-brain barrier breakdown. We investigated serum and cerebrospinal fluid (CSF) antibodies to neural and tight junction proteins and environmental pollutants in 139 children ages 11.91 ± 4.2 y with high versus low air pollution exposures. We also measured metals in serum and CSF. MCMA children showed significantly higher serum actin IgG, occludin/zonulin 1 IgA, IgG, myelin oligodendrocyte glycoprotein IgG and IgM (p < 0.01), myelin basic protein IgA and IgG, S-100 IgG and IgM, and cerebellar IgG (p < 0.001). Serum IgG antibodies to formaldehyde, benzene, and bisphenol A, and concentrations of Ni and Cd were significantly higher in exposed children (p < 0.001). CSF MBP antibodies and nickel concentrations were higher in MCMA children (p = 0.03). Air pollution exposure damages epithelial and endothelial barriers and is a robust trigger of tight junction and neural antibodies. Cryptic 'self' tight junction antigens can trigger an autoimmune response potentially contributing to the neuroinflammatory and Alzheimer and Parkinson's pathology hallmarks present in megacity children. The major factor determining the impact of neural antibodies is the integrity of the blood-brain barrier. Defining the air pollution linkage of the brain/immune system interactions and damage to physical and immunological barriers with short and long term neural detrimental effects to children's brains ought to be of pressing importance for public health.