ABSTRACT
The effects of biochar application on soil nitrous oxide ï¼N2Oï¼ and methane ï¼CH4ï¼ emissions in a typical rice-vegetable rotation system in Hainan after two years were investigated. The aim was to clarify the long-term effects of biochar on greenhouse gas emissions under this modelï¼ and it provided a theoretical basis for N2O and CH4 emission reduction in rice-vegetable rotation systems in tropical regions of China. Four treatments were set up in the field experimentï¼ including no nitrogen fertilizer control ï¼CKï¼ï¼ nitrogenï¼ phosphorusï¼ and potassium fertilizer ï¼CONï¼ï¼ nitrogenï¼ phosphorusï¼ and potassium fertilizer combined with 20 t·hm-2 biochar ï¼B1ï¼ï¼ and nitrogenï¼ phosphorusï¼ and potassium fertilizer combined with 40 t·hm-2 biochar ï¼B2ï¼. The results showed thatï¼ â compared with that in the CON treatmentï¼ the B1 and B2 treatments significantly reduced N2O emissions by 32% and 54% in the early rice season ï¼P < 0.05ï¼ the same belowï¼ï¼ but the B1 and B2 treatments significantly increased N2O emissions by 31% and 81% in the late rice season. The cumulative emissions of N2O in the pepper season were significantly higher than those in the early and late rice seasonsï¼ and the B1 treatment significantly reduced N2O emissions by 35%. There was no significant difference between the B2 and CON treatments. â¡ Compared with that in the CON treatmentï¼ B1 and B2 significantly reduced CH4 emissions by 63% and 65% in the early rice seasonï¼ and the B2 treatment significantly increased CH4 emissions by 41% in the late rice season. There was no significant difference between the B1 and CON treatments. There was no significant difference in cumulative CH4 emissions between treatments in the pepper season. ⢠The late rice season contributed to the main global warming potential ï¼GWPï¼ of the rice-vegetable rotation systemï¼ and CH4 emissions determined the magnitude of GWP and greenhouse gas emission intensity ï¼GHGIï¼. After two years of biochar applicationï¼ B1 reduced the GHGI of the whole rice-vegetable rotation systemï¼ and B2 increased the GHGI and reached a significant level. Howeverï¼ the B1 and B2 treatments significantly reduced GHGI in the early rice season and pepper seasonï¼ and only the B2 treatment increased GHGI in the late rice season. ⣠Compared with that in the CON treatmentï¼ the B1 and B2 treatments significantly increased the yield of early rice by 33% and 51%ï¼ and the B1 and B2 treatments significantly increased the yield of pepper season by 53% and 81%. In the late rice seasonï¼ there was no significant difference in yield except for in the CK treatment without nitrogen fertilizer. The results showed that the magnitude of greenhouse gas emissions in the tropical rice-vegetable rotation system was mainly determined by CH4 emissions in the late rice season. After two years of biochar applicationï¼ only low biochar combined with nitrogen fertilizer had a significant emission reduction effectï¼ but high and low biochar combined with nitrogen fertilizer increased the yield of early rice and pepper crops continuously.
Subject(s)
Charcoal , Greenhouse Gases , Oryza , Greenhouse Gases/analysis , Agriculture/methods , Fertilizers/analysis , Soil , Nitrogen , China , Methane/analysis , Nitrous Oxide/analysis , Phosphorus , Vegetables , PotassiumABSTRACT
Osteoarthritis (OA) causes joint pain and disability due to the abnormal production of inflammatory cytokines and reactive oxygen species (ROS) in chondrocytes, leading to cell death and cartilage matrix destruction. Selenium (Se) intake can protect cells against oxidative damage. It is still unknown whether Se supplementation is beneficial for OA. This study investigated the effects of Se on sodium iodoacetate (MIA)-imitated OA progress in human chondrocyte cell line (SW1353 cells) and rats. The results showed that 0.3 µM of Se treatment could protect SW1353 cells from MIA-induced damage by the Nrf2 pathway by promoting the gene expression of glutathione-synthesis-related enzymes such as the glutamate-cysteine ligase catalytic subunit, the glutamate-cysteine ligase modifier subunit, and glutathione synthetase. In addition, glutathione, superoxide dismutase, glutathione peroxidase, and glutathione reductase expressions are also elevated to eliminate excessive ROS production. Moreover, Se could downregulate NF-κB, leading to a decrease in cytokines, matrix proteases, and glycosaminoglycans. In the rats, MIA-induced cartilage loss was lessened after 2 weeks of Se supplementation by oral gavage; meanwhile, glutathione synthesis was increased, and the expressions of pro-inflammatory cytokines were decreased. These results suggest that Se intake is beneficial for OA due to its effects of decreasing cartilage loss by enhancing antioxidant capacity and reducing inflammation.
Subject(s)
Cartilage, Articular , Osteoarthritis , Selenium , Humans , Rats , Animals , NF-kappa B/metabolism , Chondrocytes/metabolism , Selenium/metabolism , NF-E2-Related Factor 2/metabolism , Glutamate-Cysteine Ligase/metabolism , Reactive Oxygen Species/metabolism , Osteoarthritis/metabolism , Oxidative Stress , Cytokines/metabolism , Glutathione/metabolism , Cartilage, Articular/metabolismABSTRACT
Kiwiberry (Actinidia arguta) is a perennial fruit tree belonging to the family Actinidiaceae. Kiwiberries are known to have an extremely high concentration of sugars, phenolics, flavonoids, and vitamin C, and possess delicious taste and health-promoting properties. Numerous studies have focused on kiwiberry fruits, demonstrating that they possess a higher phytochemical content and greater antioxidant activities than other berry fruits. The purpose of this study was to compare the phytochemical content and antioxidant potential of leaf, stem, root, and fruit extracts from twelve kiwiberry cultivars grown in Wonju, Korea, characterized by a Dwa climate (Köppen climate classification). In most kiwiberry cultivars, the total phenolic (TPC) and total flavonoid (TFC) phytochemical content was significantly higher in leaf and stem tissues, while the roots exhibited higher antioxidant activity. In fruit tissues, the TPC and TFC were higher in unripe and ripe kiwiberry fruits, respectively, and antioxidant activity was generally higher in unripe than ripe fruit across most of the cultivars. Based on our results, among the 12 kiwiberry cultivars, cv. Daebo and cv. Saehan have a significantly higher phytochemical content and antioxidant activity in all of the tissue types, thus having potential as a functional food and natural antioxidant.
Subject(s)
Actinidia , Antioxidants , Antioxidants/chemistry , Plant Extracts/chemistry , Ascorbic Acid/analysis , Phenols/analysis , Fruit/chemistry , Flavonoids/analysis , Phytochemicals/chemistryABSTRACT
Alzheimer's disease (AD) is more prevalent in women than men, supposing due to the decline of estrogens in menopause, accompanied by increased gonadotropins such as luteinizing hormone (LH). We and others found that the transcription factor early growth response-1 (EGR1) regulates cholinergic function including the expression of acetylcholinesterase (AChE) and plays a significant role in cognitive decline of AD. Here we investigated in APP/PS1 mice by ovariectomy (OVX) and estradiol (E2) supplementation or inhibition of LH the effect on hippocampus-related cognition and related molecular changes. We found that OVX-associated cognitive impairment was accompanied by increased dorsal hippocampal EGR1 expression, which was rescued by downregulating peripheral LH rather than by supplementing E2. We also found in postmortem AD brains a higher expression of pituitary LH-mRNA and higher EGR1 expression in the posterior hippocampus. Both, in human and mice, there was a significant positive correlation between respectively posterior/dorsal hippocampal EGR1 and peripheral LH expression. We conclude that peripheral increased LH and increased posterior hippocampal EGR1 plays a significant role in AD pathology.
Subject(s)
Alzheimer Disease , Cognitive Dysfunction , Mice , Female , Animals , Humans , Luteinizing Hormone/metabolism , Down-Regulation , Acetylcholinesterase , Cognitive Dysfunction/genetics , Cognitive Dysfunction/metabolism , Alzheimer Disease/metabolism , Cognition , Ovariectomy , Mice, Transgenic , Disease Models, Animal , Hippocampus/metabolismABSTRACT
The ability of cartilage to regenerate and repair is limited. N-acetyl- d-glucosamine (GlcNAc) is a nutritional supplement commonly used to activate chondrocytes. To prolong the duration of action of GlcNAc and improve its curative effect after cartilage injury, a GlcNAc thermosensitive hydrogel is prepared based on Pluronic F127 (PF127). The physicochemical properties results indicate that this hydrogel is injectable and retards the release of GlcNAc. Further, the therapeutic benefits of GlcNAc hydrogel are detected through intra-articular injection in rat specimens with cartilage injury. Behavioral experiments results indicate that the rats treated with GlcNAc hydrogel had longer step lengths, smaller foot angles and slower fall times. Compared with the sham group, the expression of Sox9 was 1.5 times and the level of collagen II was 2.4 times in the hydrogel treated group. Terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) staining result confirmed that the GlcNAc hydrogel reduce apoptosis by about 50%. Our results of immunohistochemical staining, Western blotting assays and enzyme activity detection all suggested that GlcNAc hydrogel reduce the expression of cleaved-caspase3 and caspase8 (Compared to the sham group, the protein contents were reduced by about 50% in the GlcNAc hydrogel group). We also found that GlcNAc hydrogel activates autophagy through ERK signal pathway. The results of Western blotting indicated that GlcNAc hydrogel increase the levels of LC3B and Becline1 (hydrogel group & sham group, LC3B: 1.56 ± 0.07 & 1.00 ± 0.14; Becline1: 1.98 ± 0.07 & 1.00 ± 0.13). Whereas, the content of P62 reduced after GlcNAc hydrogel treatment, the relative level in sham group and hydrogel group are 1.00 ± 0.02 and 0.73 ± 0.06. Our results revealed that the number of P-ERK positive cells in the hydrogel group (57.36 ± 3.56%) was higher when compared with the sham (24.82 ± 2.72%). And, the ratio of P-ERK and ERK was higher than that in the sham group (1.48 ± 0.07 & 1.00 ± 0.08). The GlcNAc thermosensitive hydrogel is a promising and sustainable drug delivery system for intra-articular injection in the treatment of cartilage injury.
ABSTRACT
Although there have been significant advances in the treatment of heart failure in recent years, chronic heart failure remains a leading cause of cardiovascular disease-related death. Many studies have found that targeted cardiac metabolic remodeling has good potential for the treatment of heart failure. However, most of the drugs that increase cardiac energy are still in the theoretical or testing stage. Some research has found that botanical drugs not only increase myocardial energy metabolism through multiple targets but also have the potential to restore the balance of myocardial substrate metabolism. In this review, we summarized the mechanisms by which botanical drugs (the active ingredients/formulas/Chinese patent medicines) improve substrate utilization and promote myocardial energy metabolism by activating AMP-activated protein kinase (AMPK), peroxisome proliferator-activated receptors (PPARs) and other related targets. At the same time, some potential protective effects of botanical drugs on myocardium, such as alleviating oxidative stress and dysbiosis signaling, caused by metabolic disorders, were briefly discussed.
ABSTRACT
Evodia rutaecarpa, the near-ripe fruit of Euodia rutaecarpa (Juss.) Benth, Euodia rutaecarpa (Juss.) Benth. var. officinalis (Dode) Huang, or Euodia rutaecarpa (Juss.) Benth. var. bodinieri (Dode) Huang, is a famous herbal medicine with several biological activities and therapeutic values, which has been applied for abdominalgia, abdominal distension, vomiting, and diarrhea as a complementary and alternative therapy in clinic. Indole alkaloids, particularly evodiamine (EVO), rutaecarpine (RUT), and dedhydroevodiamine (DHE), are received rising attention as the major bioactivity compounds in Evodia rutaecarpa. Therefore, this review summarizes the physicochemical properties, pharmacological activities, pharmacokinetics, and therapeutic effects on gastrointestinal diseases of these three indole alkaloids with original literature collected by PubMed, Web of Science Core Collection, and CNKI up to June 2023. Despite sharing the same parent nucleus, EVO, RUT, and DHE have different structural and chemical properties, which result in different advantages of biological effects. In their wide range of pharmacological activities, the anti-migratory activity of RUT is less effective than that of EVO, and the neuroprotection of DHE is significant. Additionally, although DHE has a higher bioavailability, EVO and RUT display better permeabilities within blood-brain barrier. These three indole alkaloids can alleviate gastrointestinal inflammatory in particular, and EVO also has outstanding anti-cancer effect, although clinical trials are still required to further support their therapeutic potential.
Subject(s)
Evodia , Gastrointestinal Diseases , Plants, Medicinal , Humans , Evodia/chemistry , Indole Alkaloids/pharmacology , Indole Alkaloids/therapeutic use , Plants, Medicinal/chemistry , Plant Extracts/pharmacology , Plant Extracts/therapeutic use , Plant Extracts/analysis , Gastrointestinal Diseases/drug therapy , Fruit/chemistryABSTRACT
BACKGROUND: Triple negative breast cancer (TNBC) is a major subtype of breast cancer, with limited therapeutic drugs in clinical. Epidermal growth factor receptor (EGFR) is reported to be overexpressed in various TNBC cells. Cantharidin is an effective ingredient in many clinical traditional Chinese medicine preparations, such as Delisheng injection, Aidi injection, Disodium cantharidinate and vitamin B6 injection. Previous studies showed that cantharidin had satisfactory pharmacological activity on a variety of tumors. In this study, we aimed to study the therapeutic potential of cantharidin for TNBC treatment by targeting EGFR, and expound its novel regulator miR-607. METHODS: The effect of cantharidin on breast cancer in vivo was evaluated by 4T1 mice model. Then the effects of cantharidin on TNBC cells was assessed by the MTT, colony formation, and AnnexinV-PE/7AAD staining. Cantharidin acts on EGFR were verified using the cell membrane chromatography, RT-PCR, Western blotting, MTT, and so on. Mechanistic studies were explored by dual-luciferase report assay, RT-PCR, western blotting, and immunofluorescence staining assay. RESULTS: Cantharidin inhibited TNBC cell growth and induce apoptosis by targeting EGFR. miR-607 was a novel EGFR regulator and exhibited suppressive functions on TNBC cell behaviors. Mechanistic study showed that cantharidin blocked the downstream PI3K/AKT/mTOR and ERK/MAPK signaling pathway. CONCLUSION: Our results revealed that cantharidin may be served as a potential candidate for TNBC treatment by miR-607-mediated downregulation of EGFR.
Subject(s)
MicroRNAs , Triple Negative Breast Neoplasms , Animals , Mice , Humans , Cantharidin , Down-Regulation , Phosphatidylinositol 3-Kinases , ErbB Receptors , ApoptosisABSTRACT
In this study, manganese-doped albumin-gelatin composite nanogels (MAGN) were prepared and used to load berberine (Ber) for the treatment of gouty arthritis (GA). The nanodrug delivery system (Ber-MAGN) can target inflammatory joints due to the intrinsic high affinity of albumin for SPARC, which is overexpressed at the inflammatory site of GA. Characterization of the pharmaceutical properties in vitro showed that Ber-MAGN had good dispersion, and the particle size was 121 ± 10.7 nm. The sustained release effect significantly improved the bioavailability of berberine. In vitro and in vivo experimental results showed that Ber-MAGN has better therapeutic effects in relieving oxidative stress and suppressing inflammation. Therefore, Ber-MAGN, as a potential pharmaceutical preparation for GA, provides a new reference for the clinical treatment plan of GA.
Subject(s)
Arthritis, Gouty , Berberine , Rats , Animals , Arthritis, Gouty/drug therapy , Berberine/pharmacology , Gelatin , Manganese , Nanogels/therapeutic useABSTRACT
Spinal cord injury is an impact-induced disabling condition. A series of pathological changes after spinal cord injury (SCI) are usually associated with oxidative stress, inflammation, and apoptosis. These pathological changes eventually lead to paralysis. The short half-life and low bioavailability of many drugs also limit the use of many drugs in SCI. In this study, we designed nanovesicles derived from macrophages encapsulating selenium nanoparticles (SeNPs) and metformin (SeNPs-Met-MVs) to be used in the treatment of SCI. These nanovesicles can cross the blood-spinal cord barrier (BSCB) and deliver SeNPs and Met to the site of injury to exert anti-inflammatory and reactive oxygen species scavenging effects. Transmission electron microscopy (TEM) images showed that the SeNPs-Met-MVs particle size was approximately 125 ± 5 nm. Drug release assays showed that Met exhibited sustained release after encapsulation by the macrophage cell membrane. The cumulative release was approximately 80% over 36 h. In vitro cellular experiments and in vivo animal experiments demonstrated that SeNPs-Met-MVs decreased reactive oxygen species (ROS) and malondialdehyde (MDA) levels, increased superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) activities, and reduced the expression of inflammatory (TNF-α, IL-1ß, and IL-6) and apoptotic (cleaved caspase-3) cytokines in spinal cord tissue after SCI. In addition, motor function in mice was significantly improved after SeNPs-Met-MVs treatment. Therefore, SeNPs-Met-MVs have a promising future in the treatment of SCI.
Subject(s)
Metformin , Nanoparticles , Selenium , Spinal Cord Injuries , Mice , Animals , Selenium/pharmacology , Selenium/therapeutic use , Reactive Oxygen Species/metabolism , Metformin/pharmacology , Metformin/therapeutic use , Spinal Cord Injuries/drug therapy , Spinal Cord Injuries/metabolism , Spinal Cord Injuries/pathology , Antioxidants/pharmacology , Antioxidants/therapeutic use , Antioxidants/metabolism , Macrophages/metabolism , Macrophages/pathology , Cell Membrane/metabolism , Cell Membrane/pathologyABSTRACT
OBJECTIVE: To observe the effect of electroacupuncture(EA) on activities of A2 type astrocytes(A2s)and A1 type astrocytes (A1s) , expressions of neurofilament protein 200 (NF-200, a marker of axon regeneration), nexin 1(NL1, a marker of synaptic regeneration), and regeneration of Nissl bodies in rats with spinal cord injury (SCI), so as to explore its mechanisms underlying improvement of SCI. METHODS: A total of 75 male SD rats were rando-mized into sham operation, model, antibody neutralizing (AN), EA and EA+AN groups, with 15 rats in each group. The SCI model was established by using an infinite field impactor to deliver an about 200 k dyne weight onto the exposed spinal cord after making a dorsal laminectomy at vertebral level T10. EA (2 Hz, 1 mA) was applied to"Dazhui"(GV14) and "Mingmen"(GV4) for 20 min, once daily for 28 days. After modeling, intraspinal injection of neutralizing antibodies IL-1α, TNF-α and complement 1q (C1q, 2 µL) to the injured spinal locus for inhibition of A1 type astrocytes (A1s) was conducted on the 1st, 7th , 14th and 21st day for rats of AN and EA+AN groups. BBB rating scale was used to evaluate hindlimb locomotor function on day 1, 7, 14, 21 and 28 after modeling. The activation of A2s (its specific marker S100a10), astrocyte (its specific marker glial fibrillary acidic protein, GFAP), and A1s (its specific marker C3) in the spinal cord was detected by immunofluorescence, and the protein expressions of NF-200 and NL1 in the spinal cord detected by Western blot and immunohistochemistry, separately, and the neuronal regeneration was observed after Nissl staining. RESULTS: After SCI, the BBB scores at 1 , 7, 14, 21 and 28 day, and the immunoactivity of NL1 and NF-200 were significantly decreased (P<0.01), and the fluorescence intensity of double labelled S100a10 (A2s)/GFAP and C3, and the expression of NF-200 were considerably increased in the model group (P<0.05, P<0.01). In contrast to the model group, the BBB scores at 7, 14, 21 and 28 day, and the immunoactivity of NL1 and NF-200, and the fluorescence intensity of A2s/GFAP in the AN, EA and AN+EA groups, and the expressions of NL1 in the EA and AN+EA groups, and expression of NF-200 protein in the AN+EA group were evidently increased (P<0.05, P<0.01), and the fluorescence intensity of C3 was strikingly decreased in the EA group (P<0.01). The effect of AN+EA was significantly superior to that of single AN and EA in increasing BBB scores at 14, 21 and 28 day, and in up-regulating the immunoactivity of NF-200(P<0.01, P<0.05). Nissl staining showed damaged structure of the gray matter of the spinal cord, atrophy of the Nissl body, and pyknosis of neurons, which was milder in the AN and EA groups, particularly in the AN+EA group. CONCLUSION: EA at GV14 and GV4 may promote activation of A2s and promote regeneration of axons and synapses in SCI model rats.
Subject(s)
Electroacupuncture , Spinal Cord Injuries , Animals , Male , Rats , Axons , Nerve Regeneration/genetics , Spinal Cord Injuries/genetics , Spinal Cord Injuries/therapy , Rats, Sprague-DawleyABSTRACT
Aflatoxin B1(AFB1) is the main secondary metabolite produced by Aspergillus flavus, which is highly toxic, carcinogenic, mutagenic and teratogenic. It can induce immune imbalance in animals or humans. Penthorum chinense Pursh (PCP) is a traditional herbal plant that has been used as a hepatoprotective drug with a long history in China. Based on the theory of traditional Chinese Medicine, we prepared Penthorum chinense Pursh Compound (PCPC) by combining four herbal medicines: 5 g Penthorum chinense Pursh, 5 g Radix bupleuri, 1 g Artemisia capillaris Thunb and 1 g Radix glycyrrhizae. The role of the Penthorum chinense Pursh Compound (PCPC) in preventing AFB1-induced immune imbalance in broiler chickens was studied. A total of 180 broiler chickens were equally distributed in six groups: controls, AFB1, YCHD and high-, medium- and low-dose PCPC treatment groups. After 28 days, broilers were anesthetized, and serum spleen and thymus samples were collected for analysis. Results show that AFB1 significantly increased and decreased the relative organ weight of the spleen and thymus, respectively. Pathological section of hematoxylin/eosin (H&E) stained spleen sections showed that AFB1 resulted in splenic tissue damage. Both the serum levels of Immunoglobulin A (IgA) and Immunoglobulin G (IgG) were suppressed in the AFB1 group. IL-6 was elevated in the AFB1 group. The balance between pro-inflammatory cytokines (IFN-γ and IL-2) and anti-inflammatory cytokine (IL-4) was disturbed by AFB1. The apoptosis-related protein and JAK/STAT pathway-related gene expression indicated that AFB1-induced apoptosis via JAK/STAT pathway. PCPC has proven its immunoprotective effects by preventing AFB1-induced immune imbalance. PCPC can be applied as a novel immune-modulating medicine in broiler chickens. It can be applied as a novel immune modulator in veterinary clinical practice.
ABSTRACT
Yangzheng Mixture is a traditional Chinese medicine used in clinical practice as an adjuvant therapy for tumors. However, little is known about its active components in tumor treatment. The purpose of this study was to explore the potential anti-tumor components of Yangzheng Mixture to better promote its clinical application. Using LC-MS/MS, 43 components were detected in concentrated Yangzheng Mixture. Six components, comprising astragaloside, calycosin, formononetin, isoquercitrin, ononin, and calycosin-7-O-ß-D-glucoside, were identified in rat plasma. The cancer cell absorption assay showed that the intracellular concentration of four components, calycosin, calycosin-7-O-ß-D-glucoside, formononetin, and ononin, increased with extended incubation time and demonstrated potential anti-tumor effects. The MTT assay results confirmed that Yangzheng Mixture inhibited different tumor cells proliferation. Additionally, the colony formation assay, flow cytometry analysis and wound healing displayed that Yangzheng Mixture and a combination of four components could inhibit colony formation, arrest the cell cycle and impair cell migration of tumor cells, including HCT-116, MHCC-97L, MCF-7 and NCI-H1299. In summary, our study highlighted the plausible application of Yangzheng Mixture as a potential adjuvant treatment for tumors. Furthermore, it identified effective anti-tumor components and provided evidences for the further clinical application of Yangzheng Mixture.
ABSTRACT
The present study aimed to explore the main active components and underlying mechanisms of Marsdenia tenacissima in the treatment of ovarian cancer(OC) through network pharmacology, molecular docking, and in vitro cell experiments. The active components of M. tenacissima were obtained from the literature search, and their potential targets were obtained from SwissTargetPrediction. The OC-related targets were retrieved from Therapeutic Target Database(TTD), Online Mendelian Inheritance in Man(OMIM), GeneCards, and PharmGKB. The common targets of the drug and the disease were screened out by Venn diagram. Cytoscape was used to construct an "active component-target-disease" network, and the core components were screened out according to the node degree. The protein-protein interaction(PPI) network of the common targets was constructed by STRING and Cytoscape, and the core targets were screened out according to the node degree. GO and KEGG enrichment analyses of potential therapeutic targets were carried out with DAVID database. Molecular docking was used to determine the binding activity of some active components to key targets by AutoDock. Finally, the anti-OC activity of M. tenacissima extract was verified based on SKOV3 cells in vitro. The PI3K/AKT signaling pathway was selected for in vitro experimental verification according to the results of GO function and KEGG pathway analyses. Network pharmacology results showed that 39 active components, such as kaempferol, 11α-O-benzoyl-12ß-O-acetyltenacigenin B, and drevogenin Q, were screened out, involving 25 core targets such as AKT1, VEGFA, and EGFR, and the PI3K-AKT signaling pathway was the main pathway of target protein enrichment. The results of molecular docking also showed that the top ten core components showed good binding affinity to the top ten core targets. The results of in vitro experiments showed that M. tenacissima extract could significantly inhibit the proliferation of OC cells, induce apoptosis of OC cells through the mitochondrial pathway, and down-regulate the expression of proteins related to the PI3K/AKT signaling pathway. This study shows that M. tenacissima has the characteristics of multi-component, multi-target, and multi-pathway synergistic effect in the treatment of OC, which provides a theoretical basis for in-depth research on the material basis, mechanism, and clinical application.
Subject(s)
Drugs, Chinese Herbal , Marsdenia , Ovarian Neoplasms , Humans , Female , Molecular Docking Simulation , Network Pharmacology , Phosphatidylinositol 3-Kinases , Proto-Oncogene Proteins c-akt , Ovarian Neoplasms/drug therapy , Ovarian Neoplasms/genetics , Databases, Genetic , Plant Extracts , Drugs, Chinese Herbal/pharmacologyABSTRACT
ETHNOPHARMACOLOGICAL RELEVANCE: Tou Nong Powder (TNP), a classical Chinese medicinal formula originated from the Chinese Ming Dynasty, has been applied to treat skin ulcers in patients with deficient constitutions. According to theory of traditional Chinese medicine, colonic ulcers share similar pathological conditions with skin ulcers, and consequently, TNP has been applied to ulcerative colitis (UC) safely and effectively. AIM OF STUDY: To investigate whether TNP obstructs 2,4,6-trinitrobenzene sulfonic acid (TNBS) induced enteric inflammation through regulation of NLRP3 inflammasome and attenuating enteric pyroptosis. MATERIALS AND METHODS: Network pharmacology and UPLC-Q-TOF/MS were operated to identify compounds and pharmacological potential targets. The therapeutic effects of TNP were assessed on TNBS induced colitis via general symptoms (disease activity index, colonic weight and length) and histopathological observation. The NF-κB/NLRP3/Caspase-1/GSDMD signaling pathway regulation was investigated by Western blot and real time reverse transcription polymerase chain reaction (RT-qPCR). RESULTS: TNP ameliorates the disease activity index, reverses the increase of colonic weight increase, alleviates colonic shortening and colonic histopathological injury. A decrease in tumor necrosis factor α (TNF-α), diamine oxidase (DAO), intercellular adhesion molecule-1 (ICAM-1), and endo-toxin (ET) were investigated in peripheral circulation. Moreover, TNP significantly obstructed the NF-κB/NLRP3/Caspase-1/GSDMD signaling pathway. CONCLUSION: TNP displays a promising therapeutic effect on UC via suppressing NF-κB/NLRP3/Caspase-1/GSDMD signaling pathway and reducing the expression of IL-1ß and IL-18.
Subject(s)
Colitis, Ulcerative , Colitis , Humans , Inflammasomes/metabolism , NF-kappa B/metabolism , Colitis, Ulcerative/chemically induced , Colitis, Ulcerative/drug therapy , NLR Family, Pyrin Domain-Containing 3 Protein/metabolism , Powders/therapeutic use , Caspase 1/metabolism , Colitis/drug therapy , Phosphate-Binding Proteins , Pore Forming Cytotoxic Proteins/metabolismABSTRACT
BACKGROUND: An effective and safe treatment for nausea and vomiting of pregnancy (NVP) is lacking. OBJECTIVE: To assess the efficacy and safety of acupuncture, doxylamine-pyridoxine, and a combination of both in women with moderate to severe NVP. DESIGN: Multicenter, randomized, double-blind, placebo-controlled, 2 × 2 factorial trial. (ClinicalTrials.gov: NCT04401384). SETTING: 13 tertiary hospitals in mainland China from 21 June 2020 to 2 February 2022. PARTICIPANTS: 352 women in early pregnancy with moderate to severe NVP. INTERVENTION: Participants received daily active or sham acupuncture for 30 minutes and doxylamine-pyridoxine or placebo for 14 days. MEASUREMENTS: The primary outcome was the reduction in Pregnancy-Unique Quantification of Emesis (PUQE) score at the end of the intervention at day 15 relative to baseline. Secondary outcomes included quality of life, adverse events, and maternal and perinatal complications. RESULTS: No significant interaction was detected between the interventions (P = 0.69). Participants receiving acupuncture (mean difference [MD], -0.7 [95% CI, -1.3 to -0.1]), doxylamine-pyridoxine (MD, -1.0 [CI, -1.6 to -0.4]), and the combination of both (MD, -1.6 [CI, -2.2 to -0.9]) had a larger reduction in PUQE score over the treatment course than their respective control groups (sham acupuncture, placebo, and sham acupuncture plus placebo). Compared with placebo, a higher risk for births with children who were small for gestational age was observed with doxylamine-pyridoxine (odds ratio, 3.8 [CI, 1.0 to 14.1]). LIMITATION: The placebo effects of the interventions and natural regression of the disease were not evaluated. CONCLUSION: Both acupuncture and doxylamine-pyridoxine alone are efficacious for moderate and severe NVP. However, the clinical importance of this effect is uncertain because of its modest magnitude. The combination of acupuncture and doxylamine-pyridoxine may yield a potentially larger benefit than each treatment alone. PRIMARY FUNDING SOURCE: The National Key R&D Program of China and the Project of Heilongjiang Province "TouYan" Innovation Team.
Subject(s)
Acupuncture Therapy , Antiemetics , Pregnancy Complications , Pregnancy , Child , Female , Humans , Doxylamine/adverse effects , Pyridoxine/therapeutic use , Pyridoxine/adverse effects , Antiemetics/therapeutic use , Quality of Life , Vomiting/drug therapy , Vomiting/chemically induced , Nausea/drug therapy , Pregnancy Complications/drug therapy , Acupuncture Therapy/adverse effectsABSTRACT
Since lipid oxidation often causes serious food safety issues worldwide, determination of oil's oxidative deterioration becomes quite significant, which still calls for efficient analytical methods. In this work, high-pressure photoionization time-of-flight mass spectrometry (HPPI-TOFMS) was firstly introduced for rapid detection of oxidative deterioration in edible oils. Through non-targeted qualitative analysis, oxidized oils with various oxidation levels were successfully discriminated for the first time by coupling HPPI-TOFMS with the orthogonal partial least squares discriminant analysis (OPLS-DA). Furthermore, by targeted interpretation of the HPPI-TOFMS mass spectra and the subsequent regression analysis (signal intensities vs TOTOX values), good linear correlations were observed for several predominant VOCs. Those specific VOCs were promising oxidation indicators, which would play important roles as TOTOX to judge the oxidation states of tested samples. The proposed HPPI-TOFMS methodology can be used as an innovative tool for accurate and effective assessment of lipid oxidation in edible oils.
Subject(s)
Food , Oils , Mass Spectrometry , Oxidative Stress , Plant Oils/chemistryABSTRACT
OBJECTIVE: To observe the effects of electroacupuncture (EA) combined with acellular nerve allograft (ANA) on the morphological structure of spinal ganglion cells and the protein expressions of nerve growth factor (NGF) and phosphorylated protein kinase B (p-Akt) in rats with sciatic nerve injury (SNI), so as to explore the protective mechanism of EA combined with ANA on spinal ganglia. METHODS: SPF male SD rats were randomly divided into normal, model, single ANA bridging (bridging) and EA + ANA (combination) groupsï¼ with 10 rats in each group. The SNI rat model was established by right sciatic nerve transection. Rats in the bridging group were bridged with ANA to the two broken ends of injured sciatic nerves. Rats in the combination group were treated with EA at "Yanglingquan" (GB34) and "Huantiao" (GB30) 2 d after ANA bridging, with dilatational wave, frequency of 1 Hz/20 Hz, intensity of 1 mA, 15 min/d, 7 d as a course of treatment for 4 consecutive courses. Sciatic function index (SFI) was observed by footprint test. Wet weight ratio of tibialis anterior muscle was calculated after weighing. Morphology of rat spinal ganglion cells was observed after Nissl staining. The protein expressions of NGF and p-Akt were detected by immunofluorescence and Western blot. RESULTS: Compared with the normal group, the SFI and wet weight ratio of tibialis anterior muscle were significantly decreased (P<0.05), the number of Nissl bodies in spinal ganglion cells was significantly reduced (P<0.05) with dissolution and incomplete structureï¼ the protein expressions of NGF and p-Akt in ganglion cells were significantly decreased (P<0.05) in the model group. Following the interventions and in comparison with the model group, the SFI and the wet weight ratio of tibialis anterior muscle were significantly increased (P<0.05), the damage of Nissl bodies in ganglion cells was reduced and the number was obviously increased (P<0.05), and the protein expressions of NGF and p-Akt in ganglion cells were significantly increased (P<0.05) in the bridging and combination groups. Compared with the bridging group, the SFI and the wet weight ratio of tibialis anterior muscle were increased (P<0.05), the morphology of Nissl bodies in ganglion cells was more regular and the number was increased (P<0.05), the protein expressions of NGF and p-Akt in spinal ganglion cells were significantly increased (P<0.05) in the combination group. CONCLUSION: EA combined with ANA can improve the SFI and the wet weight ratio of tibialis anterior muscle in SNI rats, improve the morphology and structure of Nissl bodies in spinal ganglion cells, and increase the protein expressions of NGF and p-Akt in spinal ganglion, so as to play a protective role on spinal ganglia.
Subject(s)
Allografts , Electroacupuncture , Ganglia, Spinal , Peripheral Nerve Injuries , Sciatic Nerve , Animals , Male , Rats , Allografts/metabolism , Ganglia, Spinal/cytology , Ganglia, Spinal/metabolism , Nerve Growth Factor/genetics , Nerve Growth Factor/metabolism , Peripheral Nerve Injuries/therapy , Proto-Oncogene Proteins c-akt/genetics , Proto-Oncogene Proteins c-akt/metabolism , Rats, Sprague-Dawley , Sciatic Nerve/injuriesABSTRACT
Reasonable and standard application of sham acupuncture control is the key to determine the quality of acupuncture clinical trials, and is also a difficult problem faced by acupuncture clinical research. The UK National Institute for Health Research and the Medical Research Council jointly published the Applying Surgical Placebo in Randomised Evaluation (ASPIRE) guidelines on the application of placebo surgical operation in randomized evaluation, which includes 4 parts: rationale and ethics, design, conduct, and interpretation and translation, providing comprehensive guidance for the application of placebo controls in surgical trials. As an operational intervention, acupuncture is similar to surgery, so, ASPIRE guidelines can also provide certain guidance for the application of sham acupuncture. In the present paper, we introduce the ASPIRE guidelines, and put forward its enlightenment and reference to the application of sham acupuncture control in combination with retrospecting the current situations of sham acupuncture research. We hold that future studies should strengthen the consideration of the rationality and ethics of sham acupuncture, standardize the design of sham acupuncture control, and convey the information related to sham acupuncture to patients with appropriate descriptions.
Subject(s)
Acupuncture Therapy , Acupuncture , Humans , Practice Guidelines as TopicABSTRACT
Mortality is the most clinically serious outcome, and its prevention remains a constant struggle. This study was to assess whether intravenous or oral vitamin C (Vit-C) therapy is related to reduced mortality in adults. Data from Medline, Embase, and the Cochrane Central Register databases were acquired from their inception to 26 October 2022. All randomized controlled trials (RCTs) involving intravenous or oral Vit-C against a placebo or no therapy for mortality were selected. The primary outcome was all-cause mortality. Secondary outcomes were sepsis, COVID-19, cardiac surgery, noncardiac surgery, cancer, and other mortalities. Forty-four trials with 26540 participants were selected. Although a substantial statistical difference was observed in all-cause mortality between the control and the Vit-C-supplemented groups (p = 0.009, RR 0.87, 95% CI 0.78 to 0.97, I2 = 36%), the result was not validated by sequential trial analysis. In the subgroup analysis, mortality was markedly reduced in Vit-C trials with the sepsis patients (p = 0.005, RR 0.74, 95% CI 0.59 to 0.91, I2 = 47%), and this result was confirmed by trial sequential analysis. In addition, a substantial statistical difference was revealed in COVID-19 patient mortality between the Vit-C monotherapy and the control groups (p = 0.03, RR 0.84, 95% CI 0.72 to 0.98, I2 = 0%). However, the trial sequential analysis suggested the need for more trials to confirm its efficacy. Overall, Vit-C monotherapy does decrease the risk of death by sepsis by 26%. To confirm Vit-C is associated with reduced COVID-19 mortality, additional clinical random control trials are required.