ABSTRACT
Background: The disruption of intracranial fluid dynamics due to large unruptured cerebral arteriovenous malformation (AVM) commonly triggers a domino effect within the central nervous system. This phenomenon is frequently overlooked in prior clinic and may lead to catastrophic misdiagnoses. Our team has documented the world's first case of so-called AVM Pentalogy (AVMP) induced by a AVM. Clinical presentation and result: A 30-year-old female was first seen 9 years ago with an occasional fainting, at which time a huge unruptured AVM was discovered. Subsequently, due to progressive symptoms, she sought consultations from several prestigious neurosurgical departments in China, where all consulting neurosurgeons opted for conservation treatment due to perceived surgical risks. During the follow-up period, the patient gradually presented with hydrocephalus, empty sella, secondary Chiari malformation, syringomyelia, and scoliosis (we called as AVMP). When treated in our department, she already displayed numerous symptoms, including severe intracranial hypertension. Our team deduced that the hydrocephalus was the primary driver of her AVMP symptoms, representing the most favorable risk profile for intervention. As expected, a ventriculoperitoneal shunt successfully mitigated all symptoms of AVMP at 21-months post-surgical review. Conclusion: During the monitoring of unruptured AVM, it is crucial to remain vigilant for the development or progression of AVMP. When any component of AVMP is identified, thorough etiological studies and analysis of cascade reactions are imperative to avert misdiagnosis. When direct AVM intervention is not viable, strategically addressing hydrocephalus as part of the AVMP may serve as the critical therapeutic focus.
ABSTRACT
Our laboratory previously extracted bound polyphenols (BPP) in insoluble dietary fiber from navel orange peel (NOP-IDF), and the aim of this study was to investigate the anti-inflammatory activity and potential molecular mechanisms of BPP by establishing an LPS-induced intestinal-like Caco-2/RAW264.7 co-culture inflammation model. The results demonstrated that BPP reduced the expression of cyclooxygenase-2 (COX-2) and inducible nitric oxide synthase (iNOS), as well as the production of pro-inflammatory cytokines, nitric oxide (NO), and reactive oxidative species (ROS) during the inflammatory damage process. Furthermore, BPP alleviated the lipopolysaccharides (LPS)-induced intestinal barrier damage by attenuating the decrease in trans-epithelial electrical resistance (TEER), diamine oxidase (DAO) activity, and intestinal alkaline phosphatase (IAP) activity, as well as the downregulation of ZO-1, Occludin, and Claudin-1 protein expression levels. RNA-seq results on RAW264.7 cells in the co-culture model showed that the NF-κB and JAK-STAT pathways belonged to the most significantly affected signaling pathways in the KEGG analysis, and western blot confirmed that they are essential for the role of BPP in intestinal inflammation. Additionally, overexpression of the granulocyte-macrophage colony-stimulating factor (CSF2) gene triggered abnormal activation of the NF-κB and JAK-STAT pathways and high-level expression of inflammatory factors, while BPP effectively improved this phenomenon. The above results suggested that BPP could inhibit intestinal inflammatory injury and protect intestinal barrier integrity through CSF2-mediated NF-κB and JAK-STAT pathways.
Subject(s)
Citrus sinensis , Coculture Techniques , Dietary Fiber , Lipopolysaccharides , Polyphenols , Signal Transduction , Animals , Humans , Mice , Caco-2 Cells , Citrus sinensis/chemistry , Dietary Fiber/pharmacology , Fruit/chemistry , Granulocyte-Macrophage Colony-Stimulating Factor/metabolism , Inflammation/metabolism , Intestinal Mucosa/metabolism , Intestinal Mucosa/drug effects , Intestines/drug effects , Janus Kinases/metabolism , Lipopolysaccharides/adverse effects , NF-kappa B/metabolism , NF-kappa B/genetics , Polyphenols/pharmacology , RAW 264.7 Cells , Signal Transduction/drug effects , STAT Transcription Factors/metabolismABSTRACT
This work aimed to illuminate the mechanism of Polygonatum cyrtonema polysaccharide (PCP-80%) triggered immune activation. Results showed that PCP-80% enhanced the protein expression of COX-2 and iNOS, along with increasing the release of NO, ROS, cytokines (TNF-α, IL-6) in RAW264.7 cells. RNA-seq analysis revealed 2160 differentially expressed genes (DEGs) following PCP-80% treatment, comprising 1142 up-regulated and 1018 down-regulated genes. In addition, for investigating possible regulatory mechanisms, the NF-κB, MAPKs, and JAK-STAT signaling pathways were also chosen based on bioinformatics analysis. Furthermore, these findings were further corroborated through Western blot experiments, validating the activation of JAK-STAT (reduction of JAK1 in cells and elevation of p-STAT3 in the nucleus), MAPK (elevation of p-p38, p-ERK1/2, and p-JNK), and NF-κB (elevation of p-IκBα in cells, reduction of cytoplasmic p65, and increase of nuclear content of p-p65) in macrophage activation induced by PCP-80%. Besides, the production of NO and TNF-α was decreased by the inhibitor of the three pathways. In conclusion, these findings provide strong evidence that PCP-80% effectively modulates the immune response of macrophages, with significant involvement of the JAK-STAT, MAPKs, and NF-κB signaling pathways.
Subject(s)
NF-kappa B , Polygonum , NF-kappa B/genetics , NF-kappa B/metabolism , Polygonum/metabolism , Tumor Necrosis Factor-alpha , RNA-Seq , Polysaccharides/pharmacology , ImmunityABSTRACT
Pseudomonas fluorescens is a common spoilage causing microbe found in milk. Antibiotic preservatives may cause emergence of multidrug resistance, posing food safety related risks to public health. Phage treatment may be used as an alternative to antibiotics in controlling P. fluorescens contaminations. Here we reported that P. fluorescens phage phiGM22-3 reproduced rapidly over a broad temperature range of 4 through 30°C, and the optimum growth of phiGM22-3 occurred at 10°C, indicating that it was a psychrophilic virus. Genome analysis revealed that phiGM22-3 has a genome of 42,662 bp with an identical terminal direct repeat sequence of 328 bp and encodes 58 predicted proteins. Evidence revealed that phiGM22-3 recognized lipopolysaccharides (LPS) as receptor for infection. Additionally, two phage mutants phiMX2 and phiMX8 with different host ranges were identified in the phiGM22-3 population. Phage killing efficiency of P. fluorescens cells artificially inoculated in milk was evaluated. Phage phiGM22-3 and the cocktails containing phiMX2 and phiMX8 can lyse almost 100% bacterial cells at 4°C within 24 h. Taken together, our data indicated that the psychrophilic virus phiGM22-3 and its two mutants can efficiently inhibit bacteria growth at 4°C, showing a great potential to be used as alternatives to conventional antibiotics against P. fluorescens in refrigerated foods.
Subject(s)
Bacteriophages , Pseudomonas fluorescens , Animals , Bacteriophages/genetics , Milk/microbiology , Food Microbiology , Anti-Bacterial AgentsABSTRACT
BACKGROUND: Atractylodes chinensis (DC.) Koidz. (A. chinensis) is a perennial herbaceous plant that is widely used as a Chinese medicine herb for gastric diseases. However, the bioactive compounds of this herbal medicine have not been defined, and quality control is imperfect. OBJECTIVE: Although the method of quality evaluation method for A. chinensis by high-performance liquid chromatography (HPLC) fingerprinting has been reported in related papers, it remains unknown whether the chemical markers selected are representative of their clinical efficacy. To develop methods for qualitative analysis and improved quality evaluation of A. chinensis. METHOD: In this study, HPLC was used to establish fingerprints and conduct similarity evaluation. Principal component analysis (PCA) and orthogonal partial least squares discriminant analysis (OPLS-DA) were used to reveal the differences of these fingerprints. Network pharmacology was used to analyze the corresponding targets of the active ingredients. Meantime, an active ingredient-target-pathway network was constructed to investigate the characteristics of the medical efficacy of A. chinensis and to predict potential Q-markers. RESULTS: Combining network pharmacological effectiveness and composition specificity with the Q-marker concept, atractylodin (ATD), ß-eudesmol, atractylenolide Ι (AT-I) and atractylenolide III (AT-III) were predicted to be potential Q-markers of A. chinensis that showed anti-inflammatory, antidepressant, anti-gastric, and antiviral effects by acting on 10 core targets and 20 key pathways. CONCLUSIONS: The HPLC fingerprinting method established in this study is straightforward, and the identified four active constituents can be used as Q-markers of A. chinensis. These findings facilitate effective quality evaluation of A. chinensis and suggest this approach could be applied to evaluate the quality of other herbal medicines. HIGHLIGHTS: The fingerprints of Atractylodis rhizoma were organically combined with network pharmacology to further clarify its criteria for quality control.
Subject(s)
Atractylodes , Drugs, Chinese Herbal , Plants, Medicinal , Drugs, Chinese Herbal/pharmacology , Drugs, Chinese Herbal/chemistry , Atractylodes/chemistry , Network Pharmacology , Chromatography, High Pressure Liquid , Plants, Medicinal/chemistryABSTRACT
The aim of this work was to prepare soluble dietary fibers (SDFs) from insoluble dietary fiber of navel orange peel (NOP-IDF) by mixed solid-state fermentation (M-SDF) and to investigate the influence of fermentation modification on the structural and functional characteristics of SDF in comparison with untreated soluble dietary fiber (U-SDF) of NOP-IDF. Based on this, the contribution of two kinds of SDF to the texture and microstructure of jelly was further examined. The analysis of scanning electron microscopy indicated that M-SDF exhibited a loose structure. The analysis of scanning electron microscopy indicated that M-SDF exhibited a loose structure. In addition, M-SDF exhibited increased molecular weight and elevated thermal stability, and had significantly higher relative crystallinity than U-SDF. Fermentation modified the monosaccharide composition and ratio of SDF, as compared to U-SDF. The above results pointed out that the mixed solid-state fermentation contributed to alteration of the SDF structure. Furthermore, the water holding capacity and oil holding capacity of M-SDF were 5.68 ± 0.36 g/g and 5.04 ± 0.04 g/g, which were about six times and two times of U-SDF, respectively. Notably, the cholesterol adsorption capacity of M-SDF was highest at pH 7.0 (12.88 ± 0.15 g/g) and simultaneously exhibited better glucose adsorption capacity. In addition, jellies containing M-SDF exhibited a higher hardness of 751.15 than U-SDF, as well as better gumminess and chewiness. At the same time, the jelly added with M-SDF performed a homogeneous porous mesh structure, which contributed to keeping the texture of the jelly. In general, M-SDF displayed much excellent structural and functional properties, which could be utilized to develop functional food.
ABSTRACT
PURPOSE OF THE STUDY: Understanding self-directed learning (SDL) when using point of care information systems (POCIS) can inform educational providers of the usefulness of the system for continuing medical education (CME). Sen's capability approach can offer a unique perspective to understand SDL, which considers the extent to which individual valued learning needs can be achieved. The aim of the study was to pilot the use of a questionnaire informed by the capability approach for understanding SDL when using POCIS in the context of CME. METHODS: A semi-structured questionnaire aligned to the capability approach (Capability Approach for SDL with POCIS Questionnaire - CA-SPQ) in the context of CME was developed and implemented with 200 users of a POCIS (BMJ Best Practice). RESULTS: The response rate was 92 and 78% of users considered that their valued outcomes were achieved and that they could apply their new learning to practice. The questionnaire had high content, face, and construct validity. CONCLUSION: The CA-SPQ can offer a practical instrument to provide data and useful information for understanding SDL, when using POCIS in the context of CME. It also has the potential for adaptation to other areas of medical education.
Subject(s)
Education, Distance , Point-of-Care Systems , Humans , Education, Medical, Continuing , Learning , Information SystemsABSTRACT
Tea residues are rich in dietary fiber, which possesses excellent physicochemical and functional properties in vitro. However, the hypoglycemic effect and mechanism of dietary fiber from tea residues are not clear. The study aimed to investigate the potential hypoglycemic effect of dietary fiber obtained from tea residues fermentation (TRDF) and reveal its related mechanisms of action in terms of both intestinal flora and metabolomics. The type 2 diabetes (T2D) rat model induced by high-fat diet and streptozotocin injection was applied in this study. Four weeks of TRDF intervention could remarkably ameliorate hyperglycemia, severe oxidative stress and insulin resistance of diabetic rats. Additionally, there was a significant increase of short chain fatty acids (SCFAs) concentrations in feces of diabetic rats after TRDF intervention. Furthermore, TRDF played a positive role in relieving intestinal microbiota dysbiosis by enriching beneficial bacteria (S24-7 and Prevotellaceae) and inhibiting harmful bacteria (Desulfovibrionaceae and Clostridiaceae). Metabolomic analysis showed that TRDF improved the amino acid metabolism and citrate cycle. The study elaborated on the hypoglycemic effect and potential mechanisms of TRDF through multiple pathways of gut microbiota and metabolites, which could provide theoretical basis for TRDF as a dietary supplement to manage T2D.
Subject(s)
Diabetes Mellitus, Experimental , Diabetes Mellitus, Type 2 , Animals , Dietary Fiber , Dysbiosis , Hypoglycemic Agents/pharmacology , Metabolomics , RNA, Ribosomal, 16S/genetics , Rats , Tea/chemistryABSTRACT
This study was designed to explore the beneficial effect and mechanism of Ganoderma atrum (G. atrum) polysaccharide (PSG-1) on acrolein-induced IEC-6 cells. Our results indicated that PSG-1 significantly reduced the impairment of acrolein on cell viability, decreased oxidative stress, and enabled normal expression of tight junction (TJ) proteins that were inhibited by acrolein in IEC-6 cells. Furthermore, PSG-1 attenuated the elevation of microtubule-associated proteins light chain 3 (LC3) and Beclin 1-like protein 1 (Beclin 1) and increased the protein levels of phospho-mTOR (p-mTOR) and phospho-akt (p-akt), indicating that PSG-1 activated the mammalian target of rapamycin (mTOR) signaling pathway and alleviated acrolein-induced autophagy in IEC-6 cells. Moreover, PSG-1 markedly attenuated the acrolein-induced apoptosis, as evidenced by the increase in mitochondrial membrane potential (MMP) and B-cell lymphoma 2 (Bcl-2) expression, and the decrease in cysteine aspartate lyase (caspase)-3 and caspase-9. In addition, autophagy the inhibitor inhibited acrolein-induced TJ and apoptosis of IEC-6 cells, while the apoptosis inhibitor also inhibited acrolein-induced TJ and autophagy, suggesting that autophagy and apoptosis were mutually regulated. Taken together, the present study proved that PSG-1 could protect IEC-6 cells from acrolein-induced oxidative stress and could repair TJ by inhibiting apoptosis and autophagic flux, where autophagy and apoptosis were mutually regulated.
ABSTRACT
Neurodegenerative diseases are characterized by a massive loss of specific neurons, which can be fatal. Acrolein, an omnipresent environmental pollutant, is classified as a priority control contaminant by the EPA. Evidence suggests that acrolein is a highly active unsaturated aldehyde related to many nervous system diseases. Therefore, numerous studies have been conducted to identify the function of acrolein in neurodegenerative diseases, such as ischemic stroke, AD, PD, and MS, and its exact regulatory mechanism. Acrolein is involved in neurodegenerative diseases mainly by elevating oxidative stress, polyamine metabolism, neuronal damage, and plasma ACR-PC levels, and decreasing urinary 3-HPMA and plasma GSH levels. At present, the protective mechanism of acrolein mainly focused on the use of antioxidant compounds. This review aimed to clarify the role of acrolein in the pathogenesis of four neurodegenerative diseases (ischemic stroke, AD, PD and MS), as well as protection strategies, and to propose future trends in the inhibition of acrolein toxicity through optimization of food thermal processing and exploration of natural products.
ABSTRACT
The previous research has indicated that Ganoderma atrum polysaccharide (PSG-1) indirectly affects the immune function of dendritic cells (DCs) in intestinal-like Caco-2/DCs co-culture model, in which NF-κB and MAPK pathway play an essential role. To explore the interaction of Caco-2 in the interaction between the intestinal epithelium and its internal immune cells, the intestinal-like Caco-2/DCs co-culture model was developed. All transcripts of Caco-2 treated with or without PSG-1 were globally screened by RNA-seq. The expression of 452 genes regulated by PSG-1 was statistically significant, the counts of up-regulated and down-regulated genes were 198 and 256, respectively. According to KEGG analysis, tumor necrosis factor (TNF)-α and NF-κB signaling pathways of Caco-2 were selected to elucidate the mechanism of interaction between Caco-2/DCs induced by PSG-1. After the addition of TNF-α inhibitor Apremilast and NF-κB inhibitor BAY11-70821 in Caco-2, expression of cytokines (TNF-α, IL-6, IL-1ß, IL-10), chemokines (RANTES, MIP-1α, MCP-1), and the key proteins of MAPK and NF-κB pathways of DCs were all reduced. In summary, "dialogue" between Caco-2 and DCs was regulated by PSG-1 through TNF-α and NF-κB signaling pathways of Caco-2 in the model.