RESUMEN
Hydrogen peroxide (H2O2) overexpressed in mitochondria has been regarded as a key biomarker in the pathological processes of various diseases. However, there is currently a lack of suitable mitochondria-targetable near-infrared (NIR) probes for the visualization of H2O2 in multiple diseases, such as PM2.5 exposure-induced lung injury, hepatic ischemia-reperfusion injury (HIRI), nonalcoholic fatty liver (NAFL), hepatic fibrosis (HF), and malignant tumor tissues containing clinical cancer patient samples. Herein, we conceived a novel NIR fluorescent probe (HCy-H2O2) by introducing pentafluorobenzenesulfonyl as a H2O2 sensing unit into the NIR hemicyanine platform. HCy-H2O2 exhibits good sensitivity and selectivity toward H2O2, accompanied by a remarkable "turn-on" fluorescence signal at 720 nm. Meanwhile, HCy-H2O2 has stable mitochondria-targetable ability and permits monitoring of the up-generated H2O2 level during mitophagy. Furthermore, using HCy-H2O2, we have successfully observed an overproduced mitochondrial H2O2 in ambient PM2.5 exposure-induced lung injury, HIRI, NAFL, and HF models through NIR fluorescence imaging. Significantly, the visualization of H2O2 has been achieved in both tumor-bear mice as well as surgical specimens of cancer patients, making HCy-H2O2 a promising tool for cancer diagnosis and imaging-guided surgery.
Asunto(s)
Colorantes Fluorescentes , Peróxido de Hidrógeno , Mitocondrias , Imagen Óptica , Colorantes Fluorescentes/química , Colorantes Fluorescentes/síntesis química , Peróxido de Hidrógeno/metabolismo , Animales , Mitocondrias/metabolismo , Mitocondrias/química , Ratones , Humanos , Lesión Pulmonar/diagnóstico por imagen , Lesión Pulmonar/inducido químicamente , Lesión Pulmonar/metabolismo , Rayos InfrarrojosRESUMEN
Gut inflammation seriously affects the healthy life of patients, and has a trend of increasing incidence rate. However, the current methods for treating gut inflammation are limited to surgery and drugs, which can cause irreversible damage to patients, especially infants. As natural oligosaccharides in human breast milk, human milk oligosaccharides (HMOs) function as probiotics in treating and preventing gut inflammation: improving the abundance of the gut microbiota, increasing the gut barrier function, and reducing the gut inflammatory reaction. Meanwhile, due to the complexity and high cost of their synthesis, people are searching for functional oligosaccharides that can replace HMOs as a food additive in infants milk powder and adjuvant therapy for chronic inflammation. The purpose of this review is to summarize the therapeutic and preventive effects of HMOs and their substitute functional oligosaccharides as probiotics in gut inflammation, and to summarize the prospect of their application in infant breast milk replacement in the future.
Asunto(s)
Microbioma Gastrointestinal , Probióticos , Lactante , Femenino , Humanos , Leche Humana , Oligosacáridos/farmacología , Probióticos/uso terapéutico , Estado de SaludRESUMEN
Intracellular peroxynitrite anions (ONOO-) and microenvironments (such as viscosity and polarity) play an important role in maintaining redox homeostasis, regulating diffusion, transportation, and signal transduction in living cells. The abnormality of these factors is often closely related to various physiological/pathological processes. However, owing to the lack of suitable probes, the simultaneous visualization of ONOO-, viscosity, and polarity in ferroptosis and cancer models has not been achieved. To meet urgent needs, we presented a multifunctional near-infrared (NIR) fluorescent probe, named MQA-P, for simultaneously detecting ONOO-, viscosity, and polarity within mitochondria. The probe exhibited a remarkable turn-on response to ONOO- with the far-red emission of about 645 nm and was highly sensitive to viscosity/polarity in the NIR channel with λem > 704 nm. Facilitated by MQA-P, for the first time, we revealed that erastin-induced ferroptosis was accompanied by a significant upregulation of ONOO- and an increase of viscosity (or decrease of polarity) at the same time. Moreover, the concurrent use of ONOO-, viscosity, and polarity for the diagnosis of cancer has been successfully achieved not only at cell/tissue levels but also in tumor mice models. Compared with detecting only one factor, this simultaneous detection of multimarkers provides a more sensitive and reliable method/tool for tracking ferroptosis-related pathological processes and cancer diagnosis, holding great potential in preclinical research, medical diagnosis, and imaging-guided surgery.
Asunto(s)
Ferroptosis , Neoplasias , Animales , Ratones , Colorantes Fluorescentes , Viscosidad , Ácido Peroxinitroso , Mitocondrias , Neoplasias/diagnóstico por imagenRESUMEN
The worldwide upward trend in obesity has been dramatic, but there is a lack of effective and safe drug treatment. Marine-derived algal polysaccharides, including fucoidan, alginate, polysaccharide of Spirulina platensis (PSP), ulvan, rhamnan sulfate (RS), laminarin, agar, and carrageenan, are widely used in combination with wound healing, drug delivery, and tissue-related biomedical research engineering. Recently, the prebiotic effects of algal polysaccharides and their related derivatives have received more and more attention. In this review, we discuss the potential and challenges of algal polysaccharides and their derivatives as potential therapeutic agents for obesity and its related metabolic diseases. Relevant studies have demonstrated that a variety of algal polysaccharides can play a significant role in weight loss and treatment of obesity-related metabolic diseases by improving the composition of gut microbiota, promoting bile acid formation, and upregulating cholesterol receptors in the liver. Because of their low price, non-toxic properties, and easy availability, algal polysaccharides have the potential to be developed as weight loss products.
Asunto(s)
Enfermedades Metabólicas , Polisacáridos , Humanos , Polisacáridos/farmacología , Polisacáridos/uso terapéutico , Carragenina , Enfermedades Metabólicas/tratamiento farmacológico , Obesidad/tratamiento farmacológico , Pérdida de PesoRESUMEN
Pectin as a dietary fiber supplement has shown emerging potential in clinical ulcerative colitis (UC) adjuvant therapy. In this study, the preventive and prebiotic effects of enzymatically degraded pectic oligosaccharides (POS) were further explored in dextran sodium sulfate (DSS)-induced colitis mice. The POS supplement (400 mg kg-1) was significantly effective at improving preventive efficacy, promoting colonic epithelial barrier integrity and reducing inflammatory cytokines. Meanwhile, the changes in T regulatory (Treg) cells and T helper 17 (Th17) cells indicated that POS treatment regulated the Treg/Th17 balance. Gut microbiota analysis showed that the POS supplement reshaped the dysfunctional gut microbiota. Further Spearman's correlation coefficient analysis indicated that the changes of the gut microbiota were highly associated with modulating the epithelial barrier, promoting the development of Treg cells and suppressing the differentiation of pro-inflammatory Th17 cells. All of these results suggest that enzymatically- degraded POS is a promising therapeutic agent for UC prevention and adjuvant treatment by maintaining intestinal homeostasis.
Asunto(s)
Colitis Ulcerosa , Colitis , Microbioma Gastrointestinal , Animales , Colitis/inducido químicamente , Colitis/tratamiento farmacológico , Colitis/metabolismo , Colitis Ulcerosa/inducido químicamente , Colon/metabolismo , Citocinas/metabolismo , Sulfato de Dextran/efectos adversos , Fibras de la Dieta/metabolismo , Modelos Animales de Enfermedad , Ratones , Ratones Endogámicos C57BL , Oligosacáridos/metabolismo , Pectinas/metabolismo , Linfocitos T Reguladores , Células Th17RESUMEN
The incidence rate of ulcerative colitis (UC) has increased significantly over the past decades and it places an increasing burden on health and social systems. The current studies on UC implicate a strong correlation between host gut microbiota immunity and the pathogenesis of UC. Meanwhile, more and more functional oligosaccharides have been reported as prebiotics to alleviate UC, since many of them can be metabolized by gut microbiota to produce short-chain fatty acids (SCFAs). The present review is focused on the structure, sources and specific applications of various functional oligosaccharides related to the prevention and treatment of UC. The available evidence for the usage of functional oligosaccharides in UC treatment are summarized, including fructo-oligosaccharides (FOS), galacto-oligosaccharides (GOS), chito-oligosaccharides (COS), alginate-oligosaccharides (AOS), xylooligosaccharides (XOS), stachyose and inulin.