ABSTRACT
BACKGROUND: Nauclea officinalis (Pierre ex Pit.) Merr. & Chun (Rubiaceae) is widely used to treat respiratory diseases in China. Strictosamide is its main active component and has significant anti-inflammatory activity. However, the effects and molecular mechanisms of strictosamide in the treatment of acute lung injury (ALI) remain largely unknown. PURPOSE: This study aimed to examine the regulatory effects of strictosamide on T helper 17 cells (Th17 cells)/Regulatory T cells (Treg cells) and gut microbiota in ALI-affected mice. MATERIALS AND METHODS: The ALI model was induced using lipopolysaccharide (LPS) intraperitoneal injection. Hematoxylin-eosin (H&E) staining, the number of inflammatory cells in broncho-alveolar lavage fluid (BALF), the Wet/Dry (W/D) ratio, and myeloperoxidase (MPO) activity were utilized as evaluation indices for the therapeutic efficacy of strictosamide on ALI. Flow cytometry (FCM), enzyme-linked immune sorbent assay (ELISA), quantitative reverse transcription polymerase chain reaction (qRT-PCR), and western blotting were used to determine the regulation of strictosamide on the Th17/Treg cells and the STAT3/STAT5 signaling pathway. The analysis of gut microbiota was conducted using 16S rDNA sequencing. The verification of the relationship between the gut microbiome and immune function was conducted using Spearman analysis. RESULTS: Strictosamide attenuated inflammation on ALI induced by LPS, which reduced the levels of Th17-related factors interleukin (IL)-6 and IL-17 and increased Treg-related factors IL-10 and transforming growth factor (TGF)-ß. In the spleens and whole blood, strictosamide reduced the proportion of Th17 cells and increased the proportion of Treg cells. Furthermore, strictosamide increased Forkhead/winged helix transcription factor 3 (Foxp3) and p-STAT5 protein expression while inhibiting Retinoid-related orphan nuclear receptors-γt (RORγt) and p-STAT3 expression. Moreover, strictosamide reshaped the diversity and structure of the gut microbiota, and influence the associations between immune parameters and gut microbiota in ALI mice. CONCLUSIONS: In summary, the results of the current investigation showed that strictosamide has a therapeutic impact on LPS-induced ALI. The mechanism of action of this effect may be associated with the modulation of Th17 and Treg cells differentiation via the SATA signaling pathway, as well as the impact of the gut microbiota.
Subject(s)
Acute Lung Injury , Gastrointestinal Microbiome , Lipopolysaccharides , STAT3 Transcription Factor , T-Lymphocytes, Regulatory , Th17 Cells , Animals , Acute Lung Injury/drug therapy , T-Lymphocytes, Regulatory/drug effects , Gastrointestinal Microbiome/drug effects , Th17 Cells/drug effects , Male , Mice , STAT3 Transcription Factor/metabolism , Disease Models, Animal , Mice, Inbred BALB C , Mice, Inbred C57BL , Anti-Inflammatory Agents/pharmacology , Bronchoalveolar Lavage Fluid/cytologyABSTRACT
This study aimed to investigate the therapeutic effects of Morinda officinalis iridoid glycosides(MOIG) on paw edema and bone loss of rheumatoid arthritis(RA) rats, and analyze its potential mechanism based on ultra-high performance liguid chromatography-guadrupole time-of-flight tandem mass spectrometry(UPLC-Q-TOF-MS) serum metabolomics. RA rats were established by injecting bovin type â ¡ collagen. The collagen-induced arthritis(CIA) rats were administered drug by gavage for 8 weeks, the arthritic score were used to evaluate the severity of paw edem, serum bone metabolism biochemical parameters were measured by ELISA kits, Masson staining was used to observe the bone microstructure of the femur in CIA rats. UPLC-Q-TOF-MS was used to analyze the alteration of serum metabolite of CIA rats, principal component analysis(PCA) and partial least squares-discriminant analysis(PLS-DA) were used to screen the potential biomarkers, KEGG database analysis were used to construct related metabolic pathways. The results demonstrated that the arthritic score, serum levels of IL-6 and parameters related with bone metabolism including OCN, CTX-â , DPD and TRAP were significantly increased, and the ratio of OPG and RANKL was significantly decreased, the microstructure of bone tissue and cartilage were destructed in CIA rats, while MOIG treatments could significantly reduce arthritis score, mitigate the paw edema, reverse the changes of serum biochemical indicators related with bone metabolism, and improve the microstructure of bone tissue and cartilage of CIA rats. The non-targeted metabolomics results showed that 24 altered metabolites were identified in serum of CIA rats; compared with normal group, 13 significantly altered metabolites related to RA were identified in serum of CIA rats, mainly involving alanine, aspartate and glutamate metabolism; compared with CIA model group, MOIG treatment reversed the alteration of 15 differential metabolites, mainly involving into alanine, aspartate and glutamate metabolism, D-glutamine and D-glutamate metabolism, taurine and hypotaurine metabolism, valine, leucine and isoleucine biosynthesis. Therefore, MOIG significantly alleviated paw edema, improved the destruction of microstructure of bone and cartilage in CIA rats maybe through involving into the regulation of amino acid metabolism.
Subject(s)
Arthritis, Rheumatoid , Morinda , Rats , Animals , Iridoid Glycosides/chemistry , Morinda/chemistry , Chromatography, High Pressure Liquid , Aspartic Acid , Metabolomics , Arthritis, Rheumatoid/drug therapy , Edema , Alanine/therapeutic use , Glutamates/therapeutic use , BiomarkersABSTRACT
Polysaccharides from Pumpkin (Cucurbita moschata Duchesne) (PPs) have many pharmacological activities, including anti-oxidant, immune, and intestinal microbiota regulation. These activities have provided some reminders of its potential therapeutic effect on ulcerative colitis (UC), but this has not yet been confirmed. This study preliminarily confirmed its significant anti-UC activity superior to Salicylazosulfapyridine. The average molecular weight of PPs was 3.10â¯×â¯105â¯Da, and PPs mainly comprised Mannose, Rhamnose, Galacturonic acid, Galactosamine, Glucose, and Xylose with molar ratios of 1.58:3.51:34.54:1.00:3.25:3.02. PPs (50, 100â¯mg/kg) could significantly resist dextran sodium sulfate induced UC on C57BL/6 mice by improving gut microbiota dysbiosis, such as the changes of relative abundance of Bacteroides, Culturomica, Mucispirillum, Escherichia-Shigella, Alistipes and Helicobacter. PPs also reverse the abnormal inflammatory reaction, including abnormal level changes of TNF-α, IFN-γ, IL-1ß, IL-4, IL-6, IL-10, and IL-18. Metabolomic profiling showed that PPs supplementation resulted in the participation of PPAR and MAPK pathways, as well as the increase of 5-hydroxyindole acetic acid (5-HIAA) level. 5-HIAA also exhibited individual and synergistic anti-UC activities in vivo. Furthermore, combination of PPs and 5-HIAA could also elevate the levels of PPARγ in nuclear and inhibit MAPK/NF-ĸB pathway in the colon. This study revealed that PPs and endogenous metabolite 5-HIAA might be developed to treat UC.
Subject(s)
Colitis, Ulcerative , Colitis , Cucurbita , Gastrointestinal Microbiome , Mice , Animals , Mice, Inbred C57BL , NF-kappa B , Hydroxyindoleacetic Acid , PPAR gamma , Colitis/chemically induced , Colitis/drug therapy , Bacteroidetes , Dietary Supplements , Dextran Sulfate , Disease Models, Animal , ColonABSTRACT
As prebiotics supplemented in infant formulas (IFs), galactooligosaccharides (GOSs) also have many other biological activities; however, their Maillard reaction characteristics are still unclear. We investigated the Maillard reactivity of GOSs and their effects on advanced glycation end product (AGE) formation during IF processing. The results showed that AGE and HMF formation was temperature-dependent and reached the maximum at pH 9.0 in the Maillard reaction system of GOSs and Nα-acetyl-L-lysine. Acidic conditions accelerated HMF formation; however, protein cross-linking was more likely to occur under alkaline conditions. The degree of polymerization (DP) of GOSs had no significant effect on AGEs formation (except pyrraline); however, the greater the DP, the higher the concentration of HMF and pyrraline. Besides, compared with arginine and casein, lysine and whey protein were more prone to Maillard reaction with GOSs. GOSs promoted AGEs formation in a dose-dependent manner during the processing of IFs. These results provide a reliable theoretical basis for application of GOSs in IFs.
Subject(s)
Glycation End Products, Advanced , Maillard Reaction , Humans , Glycation End Products, Advanced/metabolism , Infant Formula , Temperature , Lysine/metabolismABSTRACT
Ethnopharmacological relevance: Pinellia ternata (Thunb.) Breit. is a well-known perennial herb that is used in traditional medicine in China, Japan and Korea. It's drawing worldwide interests in medicinal applications owing such as anti-diarrhea, lipid-lowering, anti-tumor, anti-cough, expectorant, anti-gastric ulcer, etc. Aim of the study: This review aims to provide useful information on the botany, traditional uses, phytochemistry, pharmacology, toxicity and quality control of Pinellia ternata to help increase its efficiency. In addition, this review will discuss the future research trends and development prospects of this plant. Materials and methods: Data was obtained through a systematic search of published literature and online databases such as Google Scholar, Web of Science, PubMed, Science Direct, and Sci-Finder. The botanical names were confirmed using the World Flora Online and chemical structures were drawn using the ChemBio Draw Ultra Version 19.0 Software. Results: Pinellia ternata is distributed in regions of China and other areas. Pinellia ternata and its compound preparations can be used for cough, vomiting, gastric ulcer and other diseases. Approximately 212 chemical constituents have been isolated from Pinellia ternata, including alkaloids, volatile oils, amino acids, organic acids, flavonoids, cerebrosides, phenylpropanoids and other compounds. Considerable pharmacological experiments in vitro and in vivo have demonstrated that Pinellia ternata possessed antitumor effect, antitussive effects, antiasthmatic effects, increasing resistance to gastric ulcer, and antidiarrheal effect. However, these extracts can also lead to various toxicities such as irritant toxicity, cardiotoxicity, hepatotoxicity and embryonic toxicity. Considerable experiments have demonstrated that different processing methods and suitable compatibility with other herbs can effectively reduce the toxicities and increase the efficiency of Pinellia ternata. Conclusions: Pinellia ternata is an ancient herbal medicine with a broad spectrum of pharmacological activities that has been used for thousands of years in China. Future studies should perform an in-depth analyses of the pharmacokinetics and mechanisms of toxicity of Pinellia ternata. Quality standards should be developed to correspond to the various application methods to ensure the efficacy of drugs in actual treatment.
ABSTRACT
BACKGROUND: Glucocorticoids (GC)-induced osteoporosis (GIOP) is the most common cause of secondary osteoporosis, which leads to an increased risk of fracture in patients. The inhibition of the osteoblast effect is one of the main pathological characteristics of GIOP, but without effective drugs on treatment. PURPOSE: The aim of this study was to investigate the potential effects of orcinol glucoside (OG) on osteoblast cells and GIOP mice, as well as the mechanism of the underlying molecular target protein of OG both in vitro osteoblast cell and in vivo GIOP mice model. METHODS: GIOP mice were used to determine the effect of OG on bone density and bone formation. Then, a cellular thermal shift assay coupled with mass spectrometry (CETSA-MS) method was used to identify the target of OG. Surface plasmon resonance (SPR), enzyme activity assay, molecular docking, and molecular dynamics were used to detect the affinity, activity, and binding site between OG and its target, respectively. Finally, the anti-osteoporosis effect of OG through the target signal pathway was investigated in vitro osteoblast cell and in vivo GIOP mice model. RESULTS: OG treatment increased bone mineral density (BMD) in GIOP mice and effectively promoted osteoblast proliferation, osteogenic differentiation, and mineralization in vitro. The CETSA-MS result showed that the target of OG acting on the osteoblast is the p38 protein. SPR, molecular docking assay and enzyme activity assay showed that OG could direct bind to the p38 protein and is a p38 agonist. The cellular study found that OG could promote p38 phosphorylation and upregulate the proteins expression of its downstream osteogenic (Runx2, Osx, Collagen â , Dlx5). Meanwhile, it could also inhibit the nuclear transport of GR by increasing the phosphorylation site at GR226 in osteoblast cell. In vivo GIOP mice experiment further confirmed that OG could prevent bone loss in the GIOP mice model through promoting p38 activity as well as its downstream proteins expression and activity. CONCLUSIONS: This study has established that OG could promote osteoblast activity and revise the bone loss in GIOP mice by direct binding to the p38 protein and is a p38 agonist to improve its downstream signaling, which has great potential in GIOP treatment for targeting p38. This is the first report to identify OG anti-osteoporosis targets using a label-free strategy (CETSA-MS).
Subject(s)
Glucocorticoids , Osteoporosis , Animals , Mice , Glucocorticoids/adverse effects , Osteogenesis , Glucosides/therapeutic use , Molecular Docking Simulation , Osteoporosis/chemically induced , Osteoporosis/drug therapy , Osteoporosis/metabolismABSTRACT
OBJECTIVE: To evaluate the feasibility and safety of Liuzijue exercise (LE) for the clinical effect in patients after cardiac surgery. METHODS: Totally 120 patients who underwent cardiac surgery and were admitted to the Cardiothoracic Intensive Care Unit of Nanjing Drum Tower Hospital between July and Oclober, 2022 were allocated to the LE group, the conventional respiratory training (CRT) group, and the control group by a random number table at a ratio of 1:1:1; 40 patients in each group. All patients received routine treatment and cardiac rehabilitation. LE group and CRT group respectively performed LE and CRT once a day for 30 min for 7 days. Control group did not receive specialized respiratory training. The forced vital capacity, forced expiratory volume in 1 s, peak inspiratory flow rate, peak expiratory flow rate, maximum inspiratory pressure, maximum expiratory pressure, modified Barthel index (MBI), and Hamilton Rating Scale for Anxiety (HAM-A) were evaluated before, after 3 and 7 days of intervention. In addition, the postoperative length of hospital stay (LOS) and the adverse events that occurred during the intervention period were compared. RESULTS: A total of 107 patients completed the study, 120 patients were included in the analysis. After 3 days of intervention, the pulmonary function, respiratory muscle strength, MBI and HAM-A of all 3 groups improved compared with that before the intervention (P<0.05 or P<0.01). Compared with the control group, pulmonary function and respiratory muscle strength were significantly improved in the CRT and LE groups (P<0.05 or P<0.01). MBI and HAM-A were significantly improved in the LE group compared with the control and CRT groups (P<0.05 or P<0.01). On the 7th day after intervention, the difference was still statistically significant (P<0.01), and was significantly different from that on the 3rd day (P<0.05 or P<0.01). In addition, on the 7th day of intervention, the pulmonary function and respiratory muscle strength in the LE group were significantly improved compared with those in the CRT group (P<0.01). MBI and HAM-A were significantly improved in the CRT group compared with the control group (P<0.01). There were no significant differences in postoperative LOS among the 3 groups (P>0.05). No training-related adverse events occurred during the intervention period. CONCLUSIONS: LE is safe and feasible for improving pulmonary function, respiratory muscle strength, the ability to complete activities of daily living and for relieving anxiety of patients after cardiac surgery (Registration No. ChiCTR2200062964).
Subject(s)
Activities of Daily Living , Cardiac Surgical Procedures , Humans , Breathing Exercises , Cardiac Surgical Procedures/adverse effects , Respiratory Muscles , Muscle Strength/physiologyABSTRACT
Arisaema cum Bile (Dan Nanxing in Chinese, DNX) have been employed to treat allergic asthma. However, the active components and its mechanisms remain unknown. Therefore, the systematic pharmacology approach-experimental validation was performed in this study. Each 5, 6, and 10 compounds of DNX were obtained by HPLC analysis, TCMSP, and literature report, respectively. A total of 379 targets on all these compounds were acquired from Swiss Target Prediction, and 1973 targets on allergic asthma were predicated. The KEGG enrichment analysis was performed. Furthermore, a rat model of allergic asthma was established and DNX (450 mg/kg, p.o.) was given for 2 weeks. DNX treatment prevented OVA-induced pathological changes in lung cell of irregular arrange and necrotic bronchial epithelial. It also decreased inflammatory cytokines IL-4, IL-5, and IL-13 of serum and BALF, and increased IL-12 and IFN-γ. The main MAPK signaling pathway predicted by KEGG enrichment was verified, as indicated by the decreased protein expression of JNK (p < 0.05 & p < 0.01), ERK (p < 0.05), and p38 MAPK (p < 0.01) in lung tissue. These findings indicated that DNX attenuated OVA-induced allergic asthma mainly by decreasing the MAPK signaling pathway.
Subject(s)
Arisaema , Asthma , Rats , Animals , Mice , Arisaema/metabolism , Bile , Ovalbumin/adverse effects , Network Pharmacology , Molecular Structure , Asthma/drug therapy , Asthma/chemically induced , Asthma/metabolism , Cytokines/metabolism , Mice, Inbred BALB C , Disease Models, AnimalABSTRACT
ETHNOPHARMACOLOGICAL RELEVANCE: Obesity is a common metabolic dysfunction disease, which is highly correlated with the homeostasis of gut microbiota (GM). The dysregulation of GM on energy metabolism, immune response, insulin resistance and endogenous metabolites (e.g., short chain fatty acids and secondary bile acids) can affect the occurrence and development of obesity. Herbal medicine (HM) has particular advantages and definite therapeutic effects in the prevention and treatment of obesity, but its underlying mechanism is not fully clear. AIM OF THE STUDY: In this review, the representative basic and clinical anti-obesity studies associated with the homeostasis of GM regulated by HM including active components, single herb and herbal formulae were summarized and discussed. We aim to provide a state of art reference for the mechanism research of HM in treating obesity and the further development of new anti-obesity drugs. MATERIALS AND METHODS: The relevant information was collected by searching keywords (obesity, herbal medicine, prescriptions, mechanism, GM, short chain fatty acids, etc.) from scientiï¬c databases (CNKI, PubMed, SpringerLink, Web of Science, SciFinder, etc.). RESULTS: GM dysbiosis did occur in obese patients and mice, whiles the intervention of GM could ameliorate the condition of obesity. HM (e.g., berberine, Ephedra sinica, Rehjnannia glutinosa, and Buzhong Yiqi prescription) has been proved to possess a certain regulation on GM and an explicit effect on obesity, but the exact mechanism of HM in improving obesity by regulating GM remains superficial. CONCLUSION: GM is involved in HM against obesity, and GM can be a novel therapeutic target for treating obesity.
Subject(s)
Anti-Obesity Agents , Gastrointestinal Microbiome , Mice , Animals , Obesity/drug therapy , Obesity/prevention & control , Anti-Obesity Agents/pharmacology , Anti-Obesity Agents/therapeutic use , Plant Extracts/pharmacology , Fatty Acids, VolatileABSTRACT
Diminished ovarian reserve (DOR), generally defined as a decreased number or quality of oocytes, has a significant impact on quality of life and fertility in women. In recent years, the incidence of DOR has been increasing and the ages of patients are younger. The search for an effective DOR treatment has emerged as one of the preeminent research topics in reproductive health. An effective DOR therapy would improve ovarian function, fertility, and quality of life in patients. In this review we evaluated DOR treatment progress both in Western medicine and Chinese medicine, and elucidated the characteristics of each treatment.
Subject(s)
Infertility, Female , Ovarian Reserve , Female , Humans , Medicine, Chinese Traditional , Quality of Life , Oocytes , Treatment Outcome , Infertility, Female/therapyABSTRACT
Excessive and persistent inflammatory responses are a potential pathological condition that can lead to diseases of various systems, including nervous, respiratory, digestive, circulatory, and endocrine systems. Cannabinoid type 2 receptor(CB2R) belongs to the G protein-coupled receptor family and is widely distributed in immune cells, peripheral tissues, and the central nervous system. It plays a role in inflammatory responses under various pathological conditions. The down-regulation of CB2R activity is an important marker of inflammation and and CB2R modulators have been shown to have anti-inflammatory effects. This study explored the relationship between CB2R and inflammatory responses, delved into its regulatory mechanisms in inflammatory diseases, and summarized the research progress on CB2R modulators from plants other than cannabis, including plant extracts and monomeric compounds, in exerting anti-inflammatory effects. The aim is to provide new insights into the prevention and treatment of inflammatory diseases.
Subject(s)
Cannabinoid Receptor Modulators , Cannabinoids , Cannabinoid Receptor Modulators/pharmacology , Cannabinoid Receptor Agonists/pharmacology , Receptors, Cannabinoid , Cannabinoids/pharmacology , Anti-Inflammatory Agents/pharmacologyABSTRACT
Traditional Chinese medicine, as a complementary and alternative medicine, has been practiced for thousands of years in China and possesses remarkable clinical efficacy. Thus, systematic analysis and examination of the mechanistic links between Chinese herbal medicine (CHM) and the complex human body can benefit contemporary understandings by carrying out qualitative and quantitative analysis. With increasing attention, the approach of network pharmacology has begun to unveil the mystery of CHM by constructing the heterogeneous network relationship of "herb-compound-target-pathway," which corresponds to the holistic mechanisms of CHM. By integrating computational techniques into network pharmacology, the efficiency and accuracy of active compound screening and target fishing have been improved at an unprecedented pace. This review dissects the core innovations to the network pharmacology approach that were developed in the years since 2015 and highlights how this tool has been applied to understanding the coronavirus disease 2019 and refining the clinical use of CHM to combat it.
Subject(s)
COVID-19 Drug Treatment , Drugs, Chinese Herbal , Humans , Drugs, Chinese Herbal/pharmacology , Drugs, Chinese Herbal/therapeutic use , Network Pharmacology , Medicine, Chinese Traditional/methods , Treatment OutcomeABSTRACT
Alternative splicing (AS) is a universal post-transcriptional regulation process in cells, and increasing evidences have validated its crucial role in tumors. We collected AS event, gene expression, and clinical data of 178 AML patients from The Cancer Genome Atlas (TCGA) project. More than 1,000 AS events were found associated with overall survival (OS), and alternate promoter (AP) events were the most significant. The expression of the KIAA0930 transcript was the most significantly different AS event selected from AP events and significantly correlated with the expression of the splicing factor (SF) polypyrimidine tract-binding protein 1 (PTBP1). Then, the roles of PTBP1 on AS of the KIAA0930 and the proliferation of AML cells were confirmed. KIAA0930 variant 1 (KIAA0930-1) was upregulated and variant 2 (KIAA0930-2) downregulated with knockdown PTBP1 expression of AML cells by specific shRNA. A low level of PTBP1 can decrease the proliferation ability of AML cells. In conclusion, the results showed that PTBP1 might be a potential target for AML therapy.
Subject(s)
Alternative Splicing , Leukemia, Myeloid, Acute , Exons , Heterogeneous-Nuclear Ribonucleoproteins/genetics , Heterogeneous-Nuclear Ribonucleoproteins/metabolism , Humans , Leukemia, Myeloid, Acute/drug therapy , Leukemia, Myeloid, Acute/genetics , Polypyrimidine Tract-Binding Protein/genetics , Polypyrimidine Tract-Binding Protein/metabolism , RNA Splicing Factors/genetics , RNA Splicing Factors/metabolism , RNA, Small InterferingABSTRACT
Macrophyte- and algae-dominated lakes (zones) are the two typical states of shallow lakes, where the source and composition of organic matter are distinct. The burial of organic matter (OM) in the sediment supports the role of lakes as carbon sinks. However, organic matter in the sediments could be further processed, influencing the carbon cycle. The post-burial metabolism of the sedimentary OM relates closely to its composition. However, information on the differences in composition remains limited, especially the molecular composition of organic matter from sediments in the macrophyte-dominated and algae-dominated lakes. In this study, sediments were collected from the macrophyte-dominated and algae-dominated zones of Taihu Lake (East Taihu Lake and Meiliang Bay, respectively), and the active pool of sedimentary OM (water soluble organic matter, WSOM) was extracted and purified. The composition of the WSOM was characterized in detail via absorption spectroscopy, fluorescent spectroscopy, infrared spectroscopy, and Fourier transform-ion cyclotron resonance mass spectrometry (FT-ICR MS). The optical index of E2:E3 showed that the molecular size of WSOM in the macrophyte-dominated zone (M-WSOM) was slightly larger than that in the algae-dominated zone (A-WSOM). Consistently, the intensity-weighted molecular weights were identified as 388.9 and 379.9, respectively, via FT-ICR MS analysis. M-WSOM was more humified than A-WSOM, as evidenced by the SUVA254 and HIX values. The FT-ICR MS results showed that the relative abundance of the condensed aromatic substance and the aromatics were 6.3% (intensity-weighted) and 7.7% for M-WSOM and 1.1% and 4.4% for A-WSOM, respectively. The excitation-emission matrix fluorescence-parallel factor analysis (EEM-PARAFAC) suggested that the protein-like component was more in A-WSOM than that in M-WSOM, and the FT-ICR MS results showed that the intensity-weighted relative abundances of peptides were 35.6% and 15.6% for A-WSOM and M-WSOM, respectively. The FT-ICR MS results further showed that the heteroatom-containing molecules were abundant in the sedimentary WSOM, i.e., 82.9% and 91.7% for M-WSOM and A-WSOM, respectively. The nitrogen-containing molecules dominated, contributing to 53.5% and 78.5% of M-WSOM and A-WSOM, respectively. There were 30.4% and 41.4% phosphorus-containing molecules in M-WSOM and A-WSOM, respectively. The phosphorus-containing molecules in M-WSOM were mainly aliphatics and highly unsaturated structures with low oxygen, whereas those in A-WSOM were mainly peptides. This study elucidated the detailed molecular composition of WSOM in the macrophyte-dominated and algae-dominated zones of Taihu Lake, which aids understanding of the carbon, nitrogen, and phosphorus biogeochemical cycles in lakes.
Subject(s)
Geologic Sediments , Lakes , China , Environmental Monitoring/methods , Geologic Sediments/chemistry , Lakes/chemistry , Nitrogen/analysis , Phosphorus/analysis , Spectrum Analysis , Water/analysisABSTRACT
BACKGROUND: Sanguinarine (SAN) is an important natural anti-inflammatory constitutes and dietary supplementation with SAN could improve the relative length of the intestine, alter gut microbiota, and enhance growth performance of pigs, broiler chickens, and cattle. However, it is unclear whether it has the therapeutic effect on ulcerative colitis (UC). PURPOSE: This study aimed to investigate the therapeutic effect of SAN on UC and explore its mechanisms of action. STUDY DESIGN AND METHODS: Several efficacy indexes of SAN on dextran sulfate sodium (DSS)-induced C57BL/6 mice were evaluated. ELISA kit and western blot analysis were used to evaluate it's anti-inflammatory effect and the mechanism of action. 16S rDNA sequencing detection was used to determine the impact of SAN on gut microbiota. RESULTS: SAN and Sulfasalazine could significantly improve the colon length, the weight loss, the symptoms and the pathological injury of colon in DSS-induced mice. Meanwhile, SAN could decrease the levels of pro-inflammatory cytokines (TNF-α, IFN-γ, IL-1ß, IL-6, IL-13 and IL-18) and increase the levels of anti-inflammatory cytokines (IL-4 and IL-10) in colon, and suppress DSS-induced high expressions of NLRP3, caspase-1 and IL-1ß. In addition, SAN (0.5, 1 µM) could inhibit the expression level of NLRP3 and the activation of caspase-1 and IL-1ß in lipopolysaccharide-stimulated THP-1 cells in non-cytotoxic doses, which was similar to that of MCC950, a specific inhibitor of NLRP3 inflammasome activation. The abundance changes of many genera such as Muribaculaceae_unclassified, Escherichia-Shigella, Lachnospiraceae_NK4A136_group and Helicobacter were also closely related to the improvement of SAN on intestinal inflammatory response. CONCLUSION: SAN exhibited therapeutic effect on DSS-induced colitis by blocking NLRP3-(Caspase-1)/IL-1ß pathway and improving intestinal microbial dysbiosis. SAN might be developed to treat UC and other disorders associated with microbial dysbiosis.
Subject(s)
Colitis, Ulcerative , Colitis , Gastrointestinal Microbiome , Animals , Anti-Inflammatory Agents/pharmacology , Benzophenanthridines , Caspase 1/metabolism , Cattle , Chickens/metabolism , Colitis/chemically induced , Colitis, Ulcerative/chemically induced , Colitis, Ulcerative/drug therapy , Colitis, Ulcerative/pathology , Colon/pathology , Cytokines , Dextran Sulfate , Dysbiosis/drug therapy , Inflammasomes/metabolism , Isoquinolines , Mice , Mice, Inbred C57BL , NLR Family, Pyrin Domain-Containing 3 Protein/metabolism , SwineABSTRACT
Jiao-Ai Decoction (JAD), a classical traditional Chinese formula composed of seven Chinese herbs, has been widely used in clinical practice for the treatment of abortion for a long time. However, the material basis and pharmacological mechanism remain unclear. An integrative method combining ultra-performance liquid chromatography coupled with mass spectrometry (UPLC-MS/MS) analysis and therapeutic effect evaluation based on the hypothalamus-pituitary-ovarian axis (HPOA) was employed to elaborate these problems. Firstly, the chemical profile of JAD was identified by UPLC-Q-TOF-MS. Secondly, the main target ingredients from JAD were determined by UPLC-T-Q-MS. Finally, the miscarriage prevention of JAD on threatened abortion pregnant rats induced by mifepristone was investigated. Threatened abortion model in rats were replicated, uterine bleeding quantity (UBQ) and histopathological sections were measured, the contents of luteinizing hormone (LH), follicular stimulating hormone (FSH), estradiol (E2) and progesterone (P) were determined by ELISA, related genes and protein expression levels were detected by RT-PCR and western blotting. As a result, a total of 101 compounds were identified and 27 ingredients were determined to evaluate the quality of JAD. In the model rats, JAD could effectively regulate the HPOA to achieve miscarriage prevention, and the mechanism might be related to the regulation of gene and protein expression on the HPOA. This work could provide a novel and valuable approach for the quality evaluation of JAD and were expected to provide ideas and methods for the basic research on the scientific application of similar traditional Chinese medicine prescriptions.
Subject(s)
Abortion, Spontaneous , Abortion, Threatened , Drugs, Chinese Herbal , Abortion, Spontaneous/drug therapy , Abortion, Threatened/drug therapy , Abortion, Threatened/prevention & control , Animals , China , Chromatography, High Pressure Liquid/methods , Chromatography, Liquid , Drugs, Chinese Herbal/analysis , Female , Humans , Pregnancy , Rats , Tandem Mass Spectrometry/methodsABSTRACT
As a common cause of liver injury, hepatic ischemia/reperfusion injury (HIRI) happens in various clinical conditions including trauma, hepatectomy and liver transplantation. Since transcription factor Yin Yang 1 (YY1) was reported to be downregulated after ischemia/reperfusion (I/R) injury, we focused on YY1 to explore its function in HIRI by functional assays like Cell Counting Kit-8 (CCK-8) assays and flow cytometry assays. The RT-qPCR assay revealed that YY1 was downregulated in hepatocytes after I/R injury. The function assays disclosed that YY1 facilitated cell viability and proliferation, but hindered cell apoptosis in hepatocytes after I/R injury. Through mechanism assays including luciferase reporter assay, RIP and RNA pulldown assay, miR-186-5p was found to bind with YY1 and promote hepatocyte apoptosis by targeting YY1. Subsequently, we verified that small nucleolar RNA host gene 1 (SNHG1) could sponge miR-186-5p to upregulate YY1. Importantly, we figured out that YY1 had a positive regulation on SNHG1. Along the way, YY1 was identified as the upstream transcription factor for SNHG1. In conclusion, our study unveiled a novel competing endogenous RNA (ceRNA) pattern of SNHG1/miR-186-5p/YY1 positive feedback loop in hepatic I/R injury, which might provide new insight into prevention of HIRI during liver transplantation or hepatic surgery.
Subject(s)
MicroRNAs , RNA, Long Noncoding , Reperfusion Injury , Apoptosis/genetics , Feedback , Humans , Ischemia , Liver/metabolism , MicroRNAs/genetics , MicroRNAs/metabolism , RNA, Long Noncoding/genetics , RNA, Long Noncoding/metabolism , Reperfusion Injury/genetics , Transcription Factors , YY1 Transcription Factor/genetics , YY1 Transcription Factor/metabolismABSTRACT
To analyze the research status of acupuncture and moxibustion for cancer at home and abroad in the past 45 years by using bibliometric and scientific knowledge map methodsï¼and explore the development trends in future. The literature of acupuncture and moxibustion for cancer was retrieved from CNKI and Web of Science (WOS) till December 31, 2020 since the database establishment, and CiteSpace and VOSviewer software were used to perform visual map analysis through cooperation network, keyword co-occurrence, keyword timeline, keyword emergence and other methods. Totally, 1 585 literature in CNKI and 1 564 literature in WOS were included, and the annual publication amount showed a fluctuating upward trend. Cooperation between countries was centered on China and the United States, and there was relatively little cooperation among different institutions. The analysis of keyword and cited literature showed that researches focused on the control of acupuncture and moxibustion therapy on cancer complications and adverse reactions of western medicine. The main research types in WOS were systematic review and randomized controlled trial (RCT), while in CNKI was review, depth studies on mechanism of acupuncture and moxibustion for cancer were rare. The concern about the quality of life of cancer patients may become research emphasis in the field of acupuncture and moxibustion for cancer in future, and the research scope tends to integrative and holistic oncology.
Subject(s)
Acupuncture Therapy , Acupuncture , Moxibustion , Neoplasms , Bibliometrics , Humans , Neoplasms/therapyABSTRACT
INTRODUCTION: Diarrhea-predominant irritable bowel syndrome (IBS-D) is a bowel disease with a high incidence. It significantly reduces the quality of life of patients and affects the patient's daily activities and mental health. No specific therapeutic medications for IBS-D have been found. Published clinical trials suggest that Chinese herbal formula Tongxie Yaofang (TXYF) for IBS-D may be effective. However, high-quality clinical evidence supporting its use in IBS-D is still lacking. This trial aims to evaluate the therapeutic effects and safety of TXYF for IBS-D in adults. METHODS/DESIGN: A randomized, multiple-blind, placebo-controlled trial will be conducted. It will consist of an 8-week intervention followed by a 3-month follow-up period. The target sample size is 96 IBS-D patients aged 18 to 65 years. The eligible participants will be randomly allocated to either TXYF or placebo group in a ratio of 1:1. Participants in the experimental group will take TXYF granules, while participants in the control group will be given TXYF placebo granules. The primary outcome will be the degree of IBS symptom severity measured using the scale of IBS symptom severity score. The secondary outcomes include: (a) stool frequency, and (b) stool consistency measured using the Bristol stool scale, (c) quality of life measured using the scale of IBS-quality of life, (d) anxiety measured using the self-rating anxiety scale, (e) depression measured by the self-rating depression scale, and (f) the safety of using TXYF and placebo. Safety monitoring and assessment will be undertaken throughout treatment. DISCUSSION: Chinese herbal formula TXYF consists of four Chinese herbs: Atractylodes macrocephala Koidz., Paeonia lactiflora Pall ., Citrus × aurantium L ., and Radix saposhnikoviae. It has been used for diarrhea for hundreds of years and may have a potential benefit in treating adults with IBS-D, but due to lack of high-quality evidence, we designed a randomized, multiple-blind, placebo-controlled trial to evaluate its therapeutic effects and safety. This trial will provide important data to guide the clinical practice of TXYF for the treatment of IBS-D in adults. TRIAL REGISTRATION: ISRCTN registry ISRCTN12453166 . Registered on 23 March 2021.