ABSTRACT
All coronaviruses known to have recently emerged as human pathogens probably originated in bats1. Here we use a single experimental platform based on immunodeficient mice implanted with human lung tissue (hereafter, human lung-only mice (LoM)) to demonstrate the efficient in vivo replication of severe acute respiratory syndrome coronavirus (SARS-CoV), Middle East respiratory syndrome coronavirus (MERS-CoV) and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), as well as two endogenous SARS-like bat coronaviruses that show potential for emergence as human pathogens. Virus replication in this model occurs in bona fide human lung tissue and does not require any type of adaptation of the virus or the host. Our results indicate that bats contain endogenous coronaviruses that are capable of direct transmission to humans. Our detailed analysis of in vivo infection with SARS-CoV-2 in human lung tissue from LoM showed a predominant infection of human lung epithelial cells, including type-2 pneumocytes that are present in alveoli and ciliated airway cells. Acute infection with SARS-CoV-2 was highly cytopathic and induced a robust and sustained type-I interferon and inflammatory cytokine and chemokine response. Finally, we evaluated a therapeutic and pre-exposure prophylaxis strategy for SARS-CoV-2 infection. Our results show that therapeutic and prophylactic administration of EIDD-2801-an oral broad-spectrum antiviral agent that is currently in phase II/III clinical trials-markedly inhibited SARS-CoV-2 replication in vivo, and thus has considerable potential for the prevention and treatment of COVID-19.
Subject(s)
COVID-19 Drug Treatment , COVID-19/prevention & control , Cytidine/analogs & derivatives , Hydroxylamines/administration & dosage , Hydroxylamines/therapeutic use , Administration, Oral , Alveolar Epithelial Cells/immunology , Alveolar Epithelial Cells/pathology , Alveolar Epithelial Cells/virology , Animals , COVID-19/immunology , Chemoprevention , Chiroptera/virology , Clinical Trials, Phase II as Topic , Clinical Trials, Phase III as Topic , Cytidine/administration & dosage , Cytidine/therapeutic use , Cytokines/immunology , Epithelial Cells/virology , Female , Heterografts , Humans , Immunity, Innate , Interferon Type I/immunology , Lung/immunology , Lung/pathology , Lung/virology , Lung Transplantation , Male , Mice , Post-Exposure Prophylaxis , Pre-Exposure Prophylaxis , SARS-CoV-2/immunology , SARS-CoV-2/pathogenicity , Virus ReplicationABSTRACT
The intestine is considered to be a vital digestive organ to absorb nutrients and is the largest immune organ, while numerous microorganisms coexist with the host. It is well known that the complex interactions between the gut microbiota and the host's immune system inevitably affect the function of other organs, creating an "axis" between them. During the past few years, a new technique based mainly on microfluidics and cell biology has been developed to emulate the structure, function, and microenvironment of the human gut, called the "gut-on-chip". This microfluidic chip provides insight into key aspects of gut function in health and disease, such as the gut-brain axis, gut-liver axis, gut-kidney axis, and gut-lung axis. In this review, we first describe the basic theory of the gut axis and the various composition and parameter monitoring of the gut microarray systems, as well as summarize the development and emerging advances in the gut-organ-on-chip, with a focus on the host-gut flora and nutrient metabolism, and highlight their role in pathophysiological studies. In addition, this paper discusses the challenges and prospects for the current development and further use of the gut-organ-on-chip platform.
Subject(s)
Gastrointestinal Microbiome , Microfluidics , Humans , Microfluidics/methods , Liver/metabolism , Lung , NutrientsABSTRACT
In this study, we investigated the protective effect of Astragaloside IV (Ast) on mouse podocytes and its possible mechanism of action by constructing a cadmium-induced mouse renal podocytes model. We investigated the effects of cadmium (Cd) toxicity on cell number, morphology, the mitochondrial status of subcellular organelles, protein and gene levels, and the protective effects of Ast by constructing a model of Cd-induced damage to mouse renal podocytes (MPC5) and giving Ast protection at the same time. The results showed that exposure of MPC5 cells to CdCl2 culture medium containing 6.25 µM concentration acted with low cell mortality, but the mortality of MPC5 cells increased with the prolongation of cadmium exposure time. Given Ast, the death rate in the low dose group (12.5 µM) was significantly reduced, while the death rate in the medium dose group (25 µM) was extremely significantly reduced. In comparison to the control group, the Cd-exposed group exhibited a significant increase of 166.7% in malondialdehyde (MDA) content and a significant decrease of 17.1% in SOD activity. The mitochondrial membrane potential was also reduced to varying degrees. However, in the Ast-protected group compared to the Cd-exposed group, the MDA content significantly decreased by 20.8%, the SOD activity decreased by 7.14%, and the mitochondrial membrane potential showed a significant increase. Fluorescence staining of mitochondrial membrane potential indicated that Cd exposure caused mitochondrial apoptosis. In the 12-h cadmium-exposed group, the protein expression of Nephrin in mice significantly decreased by 33.4%. However, the expression of the Desmin protein significantly increased by 67.8%, and the expression of the autophagy protein LC3-II significantly increased by 55.5%. Meanwhile, the expression of PINK1, a mitochondrial autophagy pathway protein, was significantly increased in the 12 h and 24 h cadmium exposure groups. The mRNA level of PINK1 was significantly increased, and that of Parkin was decreased in the 48 h cadmium exposure group. Compared to the Cd-exposed group, the Ast group showed more significant improvements in the expression of podocyte structure, functional proteins, and mitochondrial autophagy pathway proteins. The immunological assay of mitochondrial autophagic pathway proteins further indicated that Cd-induced damage to MPC5 cells might be associated with the dysregulation of mitochondrial autophagy.
Subject(s)
Cadmium , Podocytes , Mice , Animals , Cadmium/metabolism , Podocytes/metabolism , Apoptosis , Superoxide Dismutase/metabolism , Protein Kinases/metabolismABSTRACT
The golden needle mushroom (Flammulina velutiper) is one of the most productive mushrooms in the world. However, F. velutiper experiences continuous quality degradation in terms of changes in color and textural characteristics, loss of moisture, nutrition and flavor, and increased microbial populations due to its high respiratory activity during the postharvest phase. Postharvest preservation techniques, including physical, chemical and biological methods, play a vital role in maintaining postharvest quality and extending the shelf life of mushrooms. Therefore, in this study, the decay process of F. velutiper and the factors affecting its quality were comprehensively reviewed. Additionally, the preservation methods (e.g., low-temperature storage, packaging, plasma treatment, antimicrobial cleaning and 1-methylcyclopropene treatment) for F. velutiper used for the last 5 years were compared to provide an outlook on future research directions. Overall, this review aims to provide a reference for developing novel, green and safe preservation techniques for F. velutiper. © 2023 Society of Chemical Industry.
Subject(s)
Agaricales , Flammulina , Gastropoda , Animals , Flammulina/metabolism , Cold TemperatureABSTRACT
A cascade spiroannulation of 2-mercaptoquinoline-3-carbaldehydes with α,α-dicyanoalkenes as well as a cascade spiroannulation of 2-mercaptoquinoline-3-carbaldehydes aldehydes with α-bromocarbonyl compounds was investigated based on a synergistic strategy, providing a series of diverse spiro-fused heterocyclic compounds containing more different functional groups. The features of this strategy directed towards molecular complexity and diversity include step economy, mild conditions, and high bond-forming efficiency, but important polycyclic heterocyclic products, which could be transformed into potential biologically interesting heterocyclic structures.
ABSTRACT
INTRODUCTION: Amblyopia always presents with monocular and binocular dysfunction. In this study, we aim to investigate the efficacy of alternative occlusion using liquid crystal glasses versus continuous occlusion therapy using traditional patches for treating amblyopia. METHODS: Eligible subjects with anisometropic amblyopia were randomized into 2 groups: alternative flicker glass (AFG) or patching group. In the AFG group, subjects were instructed to wear the flicker glasses for 1 h a day. The AFG is a lightweight spectacle frame with liquid crystal lenses that provide direct square-wave alternating occlusion, which were preprogrammed at a temporal frequency of 7 Hz. In the patching group, the patients were prescribed to wear traditional patches for 2 h a day. The best-corrected visual acuity (BCVA), contrast sensitivity function (CSF), and stereoacuity were measured at the baseline and 3 and 12 weeks. RESULTS: In this pilot study, a total of 40 children were recruited, with 20 in the AFG group. Mean BCVA improved by 0.17 ± 0.14 logMAR (95% CI = 0.10-0.23) in the AFG group and 0.18 ± 0.18 logMAR (95% CI = 0.09-0.26) in the patching group from baseline to 12 weeks. The improvement in BCVA in both groups was significant (both p < 0.01), while there was no significant difference between the groups (p = 0.82). The CSF of both low and high spatial frequencies exhibited significant improvement at 12 weeks in the AFG group (p < 0.01, respectively) and just had a significant improvement at low spatial frequency in the patching group (p < 0.01). The stereoacuity significantly improved by 504.00 ± 848.00 (95% CI = 107.12 to 900.88) arc seconds in the AFG group (p < 0.05), while it was 263.50 ± 639.55 (95% CI = -35.82 to 562.82) arc seconds in the patching group (p > 0.05). CONCLUSION: Alternative flicker glass was effective in improving both monocular and binocular function, which was most likely achieved by reducing suppression and promoting binocular fusion. This therapy exhibited promise as an alternative method for amblyopia treatment.
Subject(s)
Amblyopia , Amblyopia/therapy , Child , Follow-Up Studies , Humans , Pilot Projects , Prospective Studies , Sensory Deprivation , Treatment Outcome , Vision, BinocularABSTRACT
OBJECTIVE: Hepatocellular carcinoma (HCC) is an aggressive malignancy with limited effective treatment options. An alternative strategy is to target cells, such as tumour-infiltrating macrophages, in the HCC tumour microenvironment. The CCL2/CCR2 axis is required for recruitment of monocytes/macrophages and is implicated in various aspects of liver pathology, including HCC. We investigated the feasibility of CCL2/CCR2 as a therapeutic target against HCC. DESIGN: CCL2 expression was analysed in two independent HCC cohorts. Growth of three murine HCC cells was evaluated in an orthotopic model, a postsurgical recurrence model and a subcutaneous model in mice after blocking CCL2/CCR2 axis by a novel CCR2 antagonist or knocking out of host CCR2. In vivo macrophage or T cell depletion and in vitro cell coculture were further conducted to investigate CCL2/CCR2-mediated crosstalk between tumour-associated macrophages (TAMs) and tumour cells. RESULT: CCL2 is overexpressed in human liver cancers and is prognostic for patients with HCC. Blockade of CCL2/CCR2 signalling with knockout of CCR2 or with a CCR2 antagonist inhibits malignant growth and metastasis, reduces postsurgical recurrence, and enhances survival. Further, therapeutic blocking of the CCL2/CCR2 axis inhibits the recruitment of inflammatory monocytes, infiltration and M2-polarisation of TAMs, resulting in reversal of the immunosuppression status of the tumour microenvironment and activation of an antitumorous CD8+ T cell response. CONCLUSIONS: In patients with liver cancer, CCL2 is highly expressed and is a prognostic factor. Blockade of CCL2/CCR2 signalling suppresses murine liver tumour growth via activating T cell antitumour immune response. The results demonstrate the translational potential of CCL2/CCR2 blockade for treatment of HCCs.
Subject(s)
Carcinoma, Hepatocellular/immunology , Carcinoma, Hepatocellular/metabolism , Chemokine CCL2/metabolism , Liver Neoplasms, Experimental/immunology , Liver Neoplasms, Experimental/metabolism , Liver Neoplasms/immunology , Liver Neoplasms/metabolism , Macrophages/immunology , Neoplasm Recurrence, Local/prevention & control , Receptors, CCR2/metabolism , Animals , CD8-Positive T-Lymphocytes/immunology , Carcinoma, Hepatocellular/drug therapy , Cell Communication , Cell Line, Tumor , Chemokine CCL2/genetics , Coculture Techniques , Disease Models, Animal , Gene Knockout Techniques , Humans , Liver Neoplasms/drug therapy , Liver Neoplasms, Experimental/drug therapy , Lymphocyte Activation/drug effects , Lymphocyte Depletion , Lymphocytes, Tumor-Infiltrating/drug effects , Mice , Prognosis , Receptors, CCR2/antagonists & inhibitors , Receptors, CCR2/genetics , Retrospective Studies , Signal Transduction/drug effects , Tumor Escape , Tumor MicroenvironmentABSTRACT
BACKGROUND: Cadmium (Cd) is an environmental contaminant that poses risks to human and animal health. Selenium (Se), a beneficial element, alleviates the detrimental consequences of colitis and Cd toxicity. Se is found in food products as both inorganic Se (sodium selenite) and organic Se (typically Se-enriched yeast). Nano-selenium (nano-Se; a novel form of Se produced through the bioreduction of Se species) has recently garnered considerable interest, although its effects against Cd-induced enterotoxicity are poorly understood. The aim of this study was to investigate the impact of nano-selenium on mitigating cadmium toxicity and safeguarding the integrity of the intestinal barrier. METHODS: For a total of two cycles, we subjected 6-week-old C57 mice to chronic colitis by exposing them to Cd and nano-selenium for two weeks, followed by DSS water for one week. RESULTS: The application of nano-selenium mitigated the intensity of colitis and alleviated inflammation in the colon. Nano-selenium enhanced the diversity of the intestinal flora, elevated the concentration of short-chain fatty acids (SCFAs) in feces, and improved the integrity of the intestinal barrier. CONCLUSIONS: In summary, nano-Se may reduce intestinal inflammation by regulating the growth of intestinal microorganisms and protecting the intestinal barrier.
Subject(s)
Cadmium , Colitis , Gastrointestinal Microbiome , Mice, Inbred C57BL , Selenium , Animals , Colitis/chemically induced , Colitis/drug therapy , Selenium/pharmacology , Gastrointestinal Microbiome/drug effects , Mice , Colon/drug effects , Colon/metabolism , Colon/microbiology , Male , Chronic Disease , Disease Models, Animal , Nanoparticles , Fatty Acids, Volatile/metabolism , Feces/microbiology , Dextran Sulfate , Intestinal Mucosa/drug effects , Intestinal Mucosa/metabolism , Intestinal Mucosa/microbiologyABSTRACT
PURPOSE: To evaluate the effects of topical 0.05% cyclosporine A on Ocular Surface Disease Index (OSDI) score and ocular surface parameters after small incision lenticule extraction (SMILE) for myopia. METHODS: In this study, 151 patients who underwent SMILE were randomized into the control group (71 eyes) and the 0.05% cyclosporine A group (80 eyes). Both groups received standard treatment during the 1 month after SMILE. Over the next 3 months, The control group continued standard therapy (0.3% sodium hyaluronate) and the 0.05% cyclosporine A group received additional 0.05% cyclosporine A. OSDI total and subscale scores, non-invasive tear break-up time (NIBUT), tear lipid layer thickness (LLT), and tear meniscus height (TMH) were assessed preoperatively and postoperatively. RESULTS: Compared to baseline, the OSDI scores significantly increased in both groups (P < .001). The 0.05% cyclosporine A group exhibited lower OSDI total scores after administering 0.05% cyclosporine A versus the control group (P = .026). At 1 month of follow-up, NIBUT, LLT, and TMH values significantly decreased in both groups compared to baseline (P < .05). The 0.05% cyclosporine A group exhibited higher NIBUT, LLT, and TMH versus the control group, returning to preoperative values after 2 months. Overall, the OSDI total score and NIBUT values during follow-up were not significantly different between the two groups; however, the LLT and TMH values were significantly different between the two groups (P < .001 and .041, respectively) by repeated measures analysis of variance. CONCLUSIONS: Topical 0.05% cyclosporine A was effective in relieving subjective dry eye symptoms and maintaining ocular surface stability in the early postoperative period of SMILE. [J Refract Surg. 2024;40(4):e229-e238.].
Subject(s)
Dry Eye Syndromes , Keratomileusis, Laser In Situ , Myopia , Humans , Cyclosporine/therapeutic use , Myopia/surgery , Dry Eye Syndromes/diagnosis , Dry Eye Syndromes/drug therapy , Dry Eye Syndromes/etiology , TearsABSTRACT
Siraitia grosvenorii (SG), also known as Luo Han Guo or Monk fruit, boasts a significant history in food and medicine. This review delves into SG's historical role and varied applications in traditional Chinese culture, examining its phytochemical composition and the health benefits of its bioactive compounds. It further explores SG's biological activities, including antioxidant, anti-inflammatory, and antidiabetic properties and elucidates the mechanisms behind these effects. The review also highlights recent synthetic biology advances in enhancing the production of SG's bioactive compounds, presenting new opportunities for broadening their availability. Ultimately, this review emphasizes SG's value in food and medicine, showcasing its historical and cultural importance, phytochemistry, biological functions, action mechanisms, and the role of synthetic biology in its sustainable use.
Subject(s)
Cucurbitaceae , Synthetic Biology , Fruit/chemistry , Cucurbitaceae/chemistryABSTRACT
In this study, a novel polysaccharide, AAP-2S, was extracted from Auricularia auricula, and the anti-glycosylation effect of AAP-2S and its underlying mechanisms were investigated using an in vitro BSA-fructose model and a cellular model. The results demonstrated the inhibiting formation of advanced glycation end products (AGEs) in vitro by AAP-2S. Concurrently, it attenuated oxidative damage to proteins in the model, preserved protein sulfhydryl groups from oxidation, reduced protein carbonylation, prevented structural alterations in proteins, and decreased the formation of ß-crosslinked structures. Furthermore, AAP-2S demonstrated metal-chelating capabilities. GC-MS/MS-based metabolomics were employed to analyze changes in metabolic profiles induced by AAP-2S in a CML-induced HK-2 cell model. Mechanistic investigations revealed that AAP-2S could mitigate glycosylation and ameliorate cell fibrosis by modulating the RAGE/TGF-ß/NOX4 pathway. This study provides a foundational framework for further exploration of Auricularia auricular polysaccharide as a natural anti-AGEs agent, paving the way for its potential development and application as a food additive.
Subject(s)
Auricularia , Maillard Reaction , Auricularia/metabolism , Tandem Mass Spectrometry , Polysaccharides/pharmacology , Proteins , Glycation End Products, Advanced/metabolismABSTRACT
BACKGROUND: Diabetes mellitus (DM) is a chronic metabolic disease characterized by hyperglycemia, and its increasing prevalence is a global concern. Early diagnostic markers and therapeutic targets are essential for DM prevention and treatment. Pueraria, derived from kudzu root, is used clinically for various symptoms, and its active compound, Puerarin, shows promise in improving insulin resistance and reducing inflammation. PURPOSE: This study aims to evaluate the protective effects of metformin and Puerarin at different doses in an STZ-induced DM mouse model. The intricate metabolites within the serum of STZ-induced diabetic mice were subjected to thorough investigation, thus elucidating the intricate mechanism through which Puerarin demonstrates notable efficacy in the treatment of diabetes. METHODS: An STZ-induced DM mouse model is established. Mice are treated with metformin and puerarin at varying doses. Physiological, biochemical, and histomorphological assessments are performed. Metabolomics analysis is carried out on serum samples from control, DM, metformin, and medium-dose Puerarin groups. Western blot and qRT-PCR technologies are used to validate the mechanisms. RESULTS: The DM mouse model replicates abnormal blood glucose, insulin levels, physiological, biochemical irregularities, as well as liver and pancreas damage. Treatment with metformin and Puerarin restores these abnormalities, reduces organ injury, and modulates AMPK, PPARγ, mTOR, and NF-κB protein and mRNA expression. Puerarin activates the AMPK-mTOR and PPARγ-NF-κB signaling pathways, regulating insulin signaling, glucolipid metabolism, and mitigating inflammatory damage. CONCLUSION: This study demonstrates that Puerarin has the potential to treat diabetes by modulating key signaling pathways. The focus was on the finding that Puerarin has been shown to improve insulin signaling, glucolipid metabolism and attenuate inflammatory damage through the modulation of the AMPK-mTOR and PPARγ-NF-κB pathways. The discovery of Puerarin's favorable protective effect and extremely complex mechanism highlights its prospect in the treatment of diabetes and provides theoretical support for its comprehensive development and utilization.
Subject(s)
AMP-Activated Protein Kinases , Blood Glucose , Diabetes Mellitus, Experimental , Hypoglycemic Agents , Isoflavones , Metformin , NF-kappa B , PPAR gamma , Pueraria , Signal Transduction , TOR Serine-Threonine Kinases , Animals , Isoflavones/pharmacology , Diabetes Mellitus, Experimental/drug therapy , Hypoglycemic Agents/pharmacology , NF-kappa B/metabolism , TOR Serine-Threonine Kinases/metabolism , Signal Transduction/drug effects , Male , Metformin/pharmacology , PPAR gamma/metabolism , Pueraria/chemistry , Mice , Blood Glucose/drug effects , Blood Glucose/metabolism , AMP-Activated Protein Kinases/metabolism , Metabolomics , Insulin/blood , Insulin/metabolismABSTRACT
Respiratory syncytial virus (RSV) is a substantial cause of severe lower respiratory tract infections in infants, young children, older adults, and immunocompromised individuals. There is a vital need for effective therapeutics to prevent and/or treat severe RSV infection in these high-risk individuals. The development and pre-clinical testing of candidate RSV therapeutics could be accelerated by their evaluation in animals models that recapitulate bronchiolitis and bronchopneumonia; both hallmark features of severe RSV infection of humans. Previously, we demonstrated that implanted human lung tissue in humanized lung-only mice (LoM) can be infected with RSV resulting in a sustained virus replication. Here, we analyzed RSV-associated human lung pathology in the human lung implants of RSV-infected LoM. RSV infected epithelial cells lining the airway and alveolar regions of human lung implants resulting in hallmark histological features of RSV bronchiolitis and bronchopneumonia including distal airway and alveolar lumens clogged with 1) sloughed and necrotic RSV-infected epithelial cells, 2) neutrophil-containing inflammatory infiltrates, and 3) MUC5B dominated mucus secretions. We also show that treatment of LoM with a small molecule antiviral (ribavirin) or a neutralizing antibody (palivizumab) significantly suppressed and/or prevented RSV infection in vivo. Together, our data show that RSV infection of human lung implants in vivo has appropriate cellular tropism and results in hallmark pathological characteristics of severe bronchiolitis and bronchopneumonia in humans. They also offer proof-of-principle of the utility of this model to evaluate novel approaches for the prevention/treatment of RSV infection.
ABSTRACT
Selenium is an essential microelement involved in various biological processes. Selenium deficiency increases the risk of human immunodeficiency virus infection, cancer, cardiovascular disease, and inflammatory bowel disease. Selenium possesses anti-oxidant, anti-cancer, immunomodulatory, hypoglycemic, and intestinal microbiota-regulating properties. The non-linear dose-response relationship between selenium status and health effects is U-shaped; individuals with low baseline selenium levels may benefit from supplementation, whereas those with acceptable or high selenium levels may face possible health hazards. Selenium supplementation is beneficial in various populations and conditions; however, given its small safety window, the safety of selenium supplementation is still a subject of debate. This review summarizes the current understanding of the health-promoting effects of selenium on the human body, the dietary reference intake, and evidence of the association between selenium deficiency and disease.
ABSTRACT
BACKGROUND: The bark of Eucommia ulmoides (a perennial deciduous tree termed eucommia hereafter) has anti-hyperlipidemia effects due to its bioactive components. However, the slow growth of eucommia bark leads to a deficit in this resource. Studies have shown that eucommia leaf has bioactive components similar to those of eucommia bark and anti-hyperlipidemia effects. At present, the strength of the anti-hyperlipidemia effect of eucommia bark and eucommia leaf has not been reported. Their interaction with the gut microbiota and the mechanism by which the gut microbiota exerts anti-hyperlipidemia effects are unclear. PURPOSES: Through fecal microbiota transplantation (FMT) experiments, this study aimed to investigate the mechanism by which fecal bacteria suspensions containing chlorogenic acid (CGA), eucommia bark extract (EBE), and eucommia leaves extract (ELE) improve high-fat diet (HFD)-induced lipid metabolism disorders. Difference in anti-hyperlipidemia effects between EBE and ELE and exploring an eucommia bark substitute to improve the sustainable utilization of eucommia were also evaluated. RESULTS: EBE and ELE contain eight identical bioactive ingredients, and fecal bacteria suspensions containing EBE and ELE significantly improved HFD-induced lipid metabolism disorders and elevated blood glucose levels. The fecal bacteria suspension of healthy mice containing CGA, EBE, and ELE significantly reduced the relative abundance of Erysipelothrichaceae and Ruminococcaceae and promoted short chain fatty acids (SCFAs) production thereby activating the expression of the SCFA. G protein-coupled receptor 43 (GPR43) gene in colon and epididymal fat tissues. In addition, fecal bacteria suspensions of healthy mice containing CGA, EBE, or ELE significantly activated fasting-induced adipose factor (Fiaf) gene expression in colon tissue and inhibited the secretion of lipoprotein lipase (LPL) in liver tissue, thereby inhibiting the synthesis of triglycerides (TG). Changed in the Erysipelotrichaceae and Ruminococcaceae relative abundances were significantly correlated with these target genes. Thus, regulating the abundance of the Erysipelotrichaceae and Ruminococcaceae could serve as a potential target for the role of fecal bacteria suspensions of healthy mice containing CGA, EBE, or ELE in the Fiaf-LPL gut-liver axis and SCFAs-GPR43 gut-fat axis. In addition, regarding HFD-induced lipid metabolism disorders and gut microbiota structural disorders, we found no significant difference between ELE and EBE. CONCLUSIONS: Our FMT experiments evidenced that EBE and ELE improve lipid metabolism disorders by regulating the gut microbiota, providing a new pathway for treating hyperlipidemia using eucommia dietary therapy. There was no significant difference in the anti-hyperlipidemia effects of ELE and EBE; thus, eucommia leaf could replace eucommia bark in traditional Chinese medicine, so as to achieve a sustainable utilization of eucommia resources.
Subject(s)
Eucommiaceae , Gastrointestinal Microbiome , Lipid Metabolism Disorders , Mice , Animals , Diet, High-Fat/adverse effects , Lipid Metabolism , Eucommiaceae/chemistry , Lipoprotein Lipase , Plant Bark , Liver , Fatty Acids, Volatile/metabolism , Plant Extracts/therapeutic use , Lipid Metabolism Disorders/drug therapy , Lipid Metabolism Disorders/metabolismABSTRACT
BACKGROUND: Depression is one of the most serious mental illnesses worldwide that endangers the health of people. The pathogenesis of depression is complex and is associated with abnormal neurotransmitter levels, activation of the hypothalamic-pituitary-adrenal (HPA) axis, inflammation, and gut flora-related disorders. However, most of the current pharmacological therapies used to manage depression are inconsistent and are associated with side effects. Owing to their low toxicity and wide availability in nature, polysaccharides are gradually attracting attention and are being discovered to exert direct or indirect antidepressant effects. PURPOSE: In this review, we have summarized the classification, dosage, and experimental models to study polysaccharides with antidepressant effects obtained from different sources. We have also reviewed the protective effects and underlying mechanisms of these polysaccharides in depression by modulating inflammation, the HPA axis, and intestinal flora. METHODS: We searched the PubMed, Web of Science, and Google scholar databases and included studies that reported the use of polysaccharides in treating depression. RESULTS: The unique benefits of natural polysaccharides as antidepressants lie in their potential to modulate inflammation, regulate the HPA axis, and regulate intestinal flora, giving full play to their antidepressant effects via multiple pathways and targets. CONCLUSION: Natural polysaccharides may be a promising resource for use as adjuvant antidepressant therapy. Our study might therefore provide evidence for the development of polysaccharide resources as antidepressants.
Subject(s)
Depression , Hypothalamo-Hypophyseal System , Humans , Depression/drug therapy , Pituitary-Adrenal System , Antidepressive Agents/pharmacology , Antidepressive Agents/therapeutic use , Inflammation/drug therapy , Inflammation/metabolismABSTRACT
Eucommia bark contains many bioactive compounds and has anti-hyperlipidemic effects. However, due to the slow growth rate of the plant, there is a limited supply of this resource. Studies have demonstrated that Eucommia leaves contain active ingredients similar to those of Eucommia bark and also have anti-hyperlipidemic effects. It is not currently clear whether Eucommia leaf can be used as a substitute for Eucommia bark. Furthermore, their mechanism of action for anti-hyperlipidemia by improving the structure of the gut microbiota is also unclear. We aimed to determine the composition of the active ingredients in EBE and ELE by HPLC, establish an HFD-induced hyperlipidemia model, and combine fecal microbiota transplantation (FMT) experiments to investigate the mechanism of EBE/ELE anti-hyperlipidemia by modifying the structure of intestinal microbiota, as well as to compare the effects of EBE and ELE. Our results showed that EBE and ELE contained similar active ingredients and significantly alleviated lipid metabolism disorders and blood glucose levels in the HFD-induced hyperlipidemia model. In this study, EBE and ELE significantly reduced the relative abundance of Desulfovibrionaceae and Erysipelotrichaceae and significantly increased the relative abundance of Ruminococcaceae. They also promoted the production of short-chain fatty acids (SCFAs) and activated the gene expression of the SCFA receptors G protein-coupled receptor 41 (GPR41) and GPR43. In addition, EBE and ELE can significantly increase the expression of the fasting-induced adipose factor (Fiaf) gene in the colon and inhibit the secretion of lipoprotein lipase (LPL) in the liver, thereby inhibiting triglyceride (TG) synthesis. They also significantly activate the expression of GPR41 and GPR43 genes in the epididymal fat tissue, leading to reduced lipid accumulation in adipocytes. These effects on the target genes were associated with changes in the abundance of Desulfovibrionaceae, Erysipelotrichaceae, and Ruminococcaceae bacteria in the intestinal microbiota. Thus, regulating the relative abundance of these microbes may serve as prospective targets for EBE/ELE to influence the Fiaf-LPL gut-liver axis and the SCFAs-GPR41/GPR43 gut-fat axis. In addition, there was no significant difference in the anti-hyperlipidemic effects of ELE and EBE, suggesting that Eucommia leaf may be a suitable alternative to Eucommia bark for managing hyperlipidemia by regulating the structure of the intestinal microbiota. These findings suggest that Eucommia leaves have great potential for development as a functional food with lipid-lowering properties.
ABSTRACT
Lipid accumulation causes diseases such as obesity and abnormal lipid metabolism, thus impairing human health. Tea polysaccharide is one of the natural, active substances that can lower lipid levels. In this paper, an oleic-acid-induced HepG2 cell model was established. The lipid-lowering effects of a novel group of Fuzhuan brick tea polysaccharides (FTPs)-obtained from Fuzhuan brick tea-were examined in vitro. The monosaccharide composition of FTP3 was Glc, Gal, Ara, Man, Rha, GalAc, GlcAc, and Xyl with a molar ratio of 23.5:13.2:9.0:5.5:5.4:2.7:1.3:1.0, respectively. A molecular weight of 335.68 kDa was identified for FTP3. HepG2 cells treated with FTP3 achieved a prominent lipid-lowering effect compared with cells treated with oleic acid. Images of the Oil Red O staining treatment showed that FTP3-treated groups had significantly fewer red fat droplets. TC and TG levels were lower in FTP3-treated groups. FTP3 alleviated lipid accumulation in HepG2 cells, activated AMPK, and decreased the SREBP-1C and FAS protein expressions associated with fatty acid synthesis. FTP3 holds promising potential for its lipid-lowering effects.
ABSTRACT
Soil saline-alkalization is a significant constraint for soybean production. Owing to higher genetic diversity of wild soybean, we compared the proteomic landscape of saline-alkaline stress-tolerant (SWBY032) and stress-sensitive (SWLJ092) wild soybean (Glycine soja) strains under saline and saline-alkaline stress. Out of 346 differentially expressed proteins (DEPs) specifically involved in saline-alkaline stress, 159 and 133 DEPs were identified in only SWLJ092 and SWBY032, respectively. Functional annotations revealed that more ribosome proteins were downregulated in SWLJ092, whereas more membrane transporters were upregulated in SWBY032. Moreover, protein-protein interaction analysis of 133 DEPs revealed that 14 protein-synthesis- and 2 TCA-cycle-related DEPs might alter saline-alkaline tolerance by affecting protein synthesis and amino acid metabolism. Furthermore, we confirmed G. soja tonoplast intrinsic protein (GsTIP2-1 and GsTIP2-2), inositol transporter (GsINT1), sucrose transport protein (GsSUC4), and autoinhibited Ca2+-ATPase (GsACA11) as tonoplast transporters can synergistically improve saline-alkaline tolerance in soybean, possibly by relieving the inhibition of protein synthesis and amino acid metabolism. Overall, our findings provided a foundation for molecular breeding of a saline-alkaline stress-tolerant soybean.
Subject(s)
Fabaceae , Glycine max , Glycine max/metabolism , Proteomics , Fabaceae/metabolism , Soybean Proteins/metabolism , Membrane Transport Proteins/metabolism , Genotype , Amino Acids/metabolism , Glycine/metabolismABSTRACT
From Siraitia grosvenorii, a natural polysaccharide named SGP-1 was discovered, and its purity was determined to be 96.83%. Its structure is a glucan with 4-, 6- and 4,6-linked glucose units. In this paper, the sulfated derivative S-SGP of SGP-1 was prepared by the chlorosulfonic acid method. The sulfated derivatives were analyzed by Fourier transform infrared spectroscopy (FT-IR), gel permeation chromatography (GPC), and scanning electron microscopy (SEM). The degree of substitution (DS) of the polysaccharide is 0.62, and the weight average molecular weight (Mw) is 1.34 × 104 Da. While retaining the morphological characteristics of polysaccharides, S-SGP appeared a large number of spherical structures and strong intermolecular forces. The in vitro activity study of S-SGP showed that the sulfated derivatives had the ability to scavenge DPPH radicals, hydroxyl radicals and superoxide anions, and the scavenging power tended to increase with the increase in polysaccharide concentration. It can inhibit the growth of human hepatoma cells (HepG2), human breast cancer cells (MDA-MB-231) and human non-small cell lung cancer cells (A549) in vitro. In addition, the treatment of A549 cells with sulfuric acid derivatives can decrease the mitochondrial membrane potential, induce apoptosis, and alter the expression of apoptosis-related mRNA and protein.