ABSTRACT
Oligonucleotides have emerged as valuable new therapeutics. Presently, oligonucleotide manufacturing consists in a series of stepwise additions until the full-length product is obtained. Deprotection of the phosphorus backbone before cleavage and deprotection (C&D) by ammonolysis is necessary to control the 3-(2-cyanoethyl) thymidine (CNET) impurity. In this study, we demonstrate that the use of piperazine as a scavenger of acrylonitrile allows phosphorus deprotection and C&D to be combined in a single step. This reduces solvent consumption, processing time, and CNET levels. Additionally, we showed that substitution of piperazine for triethylamine in the phosphorus deprotection step of supported-synthesis leads to reduced reaction times and lower levels of CNET impurities.
Subject(s)
Oligonucleotides , Phosphorus , PiperazinesABSTRACT
Unraveling the influence of community assembly processes on soil ecosystem functioning presents a major challenge in the field of theoretical ecology, as it has received limited attention. Here, we used a series of long-term experiments spanning over 25 years to explore the assembly processes of bacterial, fungal, protist, and nematode communities using high-throughput sequencing. We characterized the soil microbial functional potential by the abundance of microbial genes associated with carbon, nitrogen, phosphorus, and sulfur cycling using GeoChip-based functional gene profiling, and determined how the assembly processes of organism groups regulate soil microbial functional potential through community diversity and network stability. Our results indicated that balanced fertilization (NPK) treatment improved the stochastic assembly of bacterial, fungal, and protist communities compared to phosphorus-deficient fertilization (NK) treatment. However, there was a nonsignificant increase in the normalized stochasticity ratio of the nematode community in response to fertilization across sites. Our findings emphasized that soil environmental factors influenced the assembly processes of the biotic community, which regulated soil microbial functional potential through dual mechanisms. One mechanism indicated that the high phosphorus levels and low soil nutrient stoichiometry may increase the stochasticity of bacterial, fungal, and protist communities and the determinism of the nematode community under NPK treatment, ultimately enhancing soil microbial functional potential by reinforcing the network stability of the biotic community. The other mechanism indicated that the low phosphorus levels and high soil nutrient stoichiometry may increase the stochastic process of the bacterial community and the determinism of the fungal, protist, and nematode communities under NK treatment, thereby enhancing soil microbial functional potential by improving the ß-diversity of the biotic community. Taken together, these results provide valuable insights into the mechanisms underlying the assembly processes of the biotic community that regulate ecosystem functioning.
Subject(s)
Ecosystem , Soil , Soil Microbiology , Bacteria/genetics , PhosphorusABSTRACT
Aluminium (Al) toxicity impedes crop growth in acidic soils and is considered the second largest abiotic stress after drought for crops worldwide. Despite remarkable progress in understanding Al resistance in plants, it is still unknown whether and how the soil microbiota confers Al resistance to crops. Here we found that a synthetic community composed of highly Al-resistant bacterial strains isolated from the rice rhizosphere increased rice yield by 26.36% in acidic fields. The synthetic community harvested rhizodeposited carbon for successful proliferation and mitigated soil acidification and Al toxicity through extracellular protonation. The functional coordination between plants and microbes offers a promising way to increase the usage of legacy phosphorus in topsoil. These findings highlight the potential of microbial tools for advancing sustainable agriculture in acidic soils.
Subject(s)
Microbiota , Oryza , Soil , Phosphorus , Aluminum/toxicity , Crops, Agricultural , AcidsABSTRACT
Long-term fertilization affects soil organic C accumulation. A growing body of research has revealed critical roles of bacteria in soil organic C accumulation, particularly through mineral-associated organic C (MAOC) formation. Protists are essential components of soil microbiome, but the relationships between MAOC formation and protists under long-term fertilization remain unclear. Here, we used cropland soil from a long-term fertilization field trial and conducted two microcosm experiments with 13C-glucose addition to investigate the effects of N and P fertilizations on MAOC formation and the relationships with protists. The results showed that long-term fertilization (especially P fertilization) significantly (P < 0.05) increased 13C-MAOC content. Compared with P-deficient treatment, P replenishment enriched the number of protists (mainly Amoebozoa and Cercozoa) and bacteria (mainly Acidobacteriota, Bacteroidota, and Gammaproteobacteria), and significantly (P < 0.001) promoted the abundances of bacterial functional genes controlling C, N, P, and S metabolisms. The community composition of phagotrophic protists prominently (P < 0.001) correlated with the bacterial community composition, bacterial functional gene abundance, and 13C-MAOC content. Co-occurrence networks of phagotrophic protists and bacteria were more connected in soil with the N inoculum added than in soil with the NP inoculum added. P replenishment strengthened bacterial 13C assimilation (i.e., 13C-phospholipid fatty acid content), which negatively (P < 0.05) correlated with the number and relative abundance of phagotrophic Cercozoa. Together, these results suggested that P fertilization boosts MAOC formation associated with phagotrophic protists. Our study paves the way for future research to harness the potential of protists to promote belowground C accrual in agroecosystems.
Subject(s)
Phosphorus , Soil , Phosphorus/metabolism , Carbon/metabolism , Soil Microbiology , Minerals/metabolism , Bacteria/genetics , Bacteria/metabolism , Fertilizers/analysis , FertilizationABSTRACT
As aging progresses, ß-amyloid (Aß) deposition and the resulting oxidative damage are key causes of aging diseases such as senior osteoporosis (SOP). Humulus lupulus L. (hops) is an important medicinal plant widely used in the food, beverage and pharmaceutical industries due to its strong antioxidant ability. In this study, APP/PS1 mutated transgenic mice and Aß-injured osteoblasts were used to evaluate the protective effects of hops extracts (HLE) on SOP. Mice learning and memory levels were assessed by the Morris water maze. Mice femurs were prepared for bone micro-structures and immunohistochemistry experiments. The deposition of Aß in the hippocampus, cortex and femurs were determined by Congo red staining. Moreover, protein expressions related to antioxidant pathways were evaluated by Western blotting. It was found that HLE markedly improved learning abilities and ameliorated memory impairment of APP/PS1 mice, as well as regulated antioxidant enzymes and bone metabolism proteins in mice serum. Micro-CT tests indicated that HLE enhanced BMD and improved micro-architectural parameters of mice femur. More importantly, it was discovered that HLE significantly reduced Aß deposition both in the brain and femur. Further in vitro results showed HLE increased the bone mineralization nodule and reduced the ROS level of Aß-injured osteoblasts. Additionally, HLE increased the expression of antioxidant related proteins Nrf2, HO-1, NQO1, FoxO1 and SOD-2. These results indicated that Humulus lupulus L. extract could protect against senior osteoporosis through inhibiting Aß deposition and oxidative stress, which provides a reference for the clinical application of hops in the prevention and treatment of SOP.
Subject(s)
Alzheimer Disease , Humulus , Osteoporosis , Plant Extracts , Animals , Mice , Alzheimer Disease/drug therapy , Amyloid beta-Peptides/metabolism , Amyloid beta-Protein Precursor/metabolism , Antioxidants/metabolism , Disease Models, Animal , Humulus/chemistry , Mice, Transgenic , Osteoblasts/metabolism , Osteoporosis/drug therapy , Osteoporosis/prevention & control , Oxidative Stress , Presenilin-1/genetics , Presenilin-1/metabolism , Plant Extracts/pharmacologyABSTRACT
Stroke patients with autonomic dysfunction are more likely to develop cardiac problems, which have been linked to lower functional outcomes and increased mortality. In this study, heart rate variability (HRV) detection paired with the Clinical Feature Scale will be utilized to elucidate the immediate impact of manual acupuncture on autonomic dysfunction of varying severity in the convalescence stroke phase. This is a randomized, single-blind, controlled clinical trial approach. At a ratio of 1:1, 60 appropriate patients will be randomly randomized into either the experimental or control group. On the basis of symptomatic treatment drugs, the experimental group will additionally undertake acupuncture therapy 3 times a week for 4 weeks, for a total of 12 times. Primary outcomes include 24-hour HRV and 60-minute HRV detection at week 4 compared with baseline. The secondary outcome is the score of clinical feature scale at week 4 compared with the baseline. Adverse events and safety indices will be recorded throughout the experiment. The SPSS V.25.0 statistical program was applied for analysis, and measurement data were expressed as meanâ ±â SD.
Subject(s)
Primary Dysautonomias , Stroke , Humans , Heart Rate/physiology , Single-Blind Method , Stroke/complications , Stroke/therapy , Stroke/diagnosis , Autonomic PathwaysABSTRACT
INTRODUCTION: Osteoporosis is closely related to iron metabolism. This study aimed to investigate whether hops extract (HLE) and its active component xanthohumol (XAN) could ameliorate bone loss caused by iron overload, and explored its potential mechanism. MATERIALS AND METHODS: Iron overload mice induced by iron dextran (ID) were used in vivo, and were treated with HLE and XAN for 3 months. Bone micro-structure and bone morphology parameters were determined by Micro-CT and TRAP staining. Bone metabolism markers and oxidation indexes in serum and bone tissue were evaluated. For in vitro experiment, bone formation indexes were determined. Moreover, the expression of key proteins in protein kinase B (Akt)/glycogen synthetase kinase 3ß (GSK3ß)/nuclear factor E2-related (Nrf2) pathway was evaluated by Western blotting. RESULTS: HLE and XAN effectively improved the bone micro-structure of the femur in mice, altered bone metabolism biomarkers, and regulated the expression of proteins related to bone metabolism. Additionally, they significantly promoted cell proliferation, runt-related gene 2 (Runx2) expression, and increased ALP activity in ID-induced osteoblasts. Moreover, HLE and XAN markedly inhibited the increase of oxidative stress caused by iron overload in vivo and in vitro. Further studies showed that they significantly up-regulated the expression of p-Akt, p-GSK3ß, nuclear-Nrf2, NAD(P)H: quinone oxidoreductase 1 (NQO1), and heme oxygenase-1 (HO-1) in ID-induced osteoblasts. CONCLUSION: These findings indicated hops and xanthohumol could ameliorate bone loss induced by iron overload via activating Akt/GSK3ß/Nrf2 pathway, which brought up a novel sight for senile osteoporosis therapy.
Subject(s)
Humulus , Iron Overload , Animals , Flavonoids , Glycogen Synthase Kinase 3 beta/metabolism , Glycogen Synthase Kinase 3 beta/pharmacology , Heme Oxygenase-1/metabolism , Heme Oxygenase-1/pharmacology , Humulus/metabolism , Iron/pharmacology , Iron Overload/drug therapy , Mice , NF-E2-Related Factor 2/genetics , NF-E2-Related Factor 2/metabolism , NF-E2-Related Factor 2/pharmacology , Oxidative Stress , Plant Extracts/pharmacology , Propiophenones , Proto-Oncogene Proteins c-akt/metabolism , Signal TransductionABSTRACT
Breast cancer is a malignant epithelial tumor of ductal or lobular origin. Breast cancer remains the most frequently diagnosed invasive cancer in women and is the leading cause of cancer-associated mortality worldwide. Epithelial-mesenchymal transition (EMT), a phenotypic process of conversion from epithelial to mesenchymal cells, allows tumor cells to acquire infiltration and metastasization properties. Therapies directed at pathways, which are primarily involved in malignant transformation, can lead to clinical implications. In recent years, EMT has gained increasing attention as a potential therapeutic target in cancer therapy. Moreover, for the past few decades, increasing numbers of studies have suggested that Traditional Chinese Medicine(TCM) compounds can significantly inhibit the growth and development of breast cancer cells through the inhibition of EMT in breast cancer cells. This review discusses some essential signaling pathways associated with EMT and summarizes the effects and mechanism of TCM components on that inhibit EMT in breast cancer therapy.
Subject(s)
Breast Neoplasms , Epithelial-Mesenchymal Transition , Humans , Medicine, Chinese TraditionalABSTRACT
Asiatic acid is a natural triterpene found in Centella asiatica that acts as an effective free radical scavenger. Our previous research showed that asiatic acid delayed porcine oocyte ageing in vitro and improved preimplantation embryo development competence in vitro; however, the protective effects of asiatic acid against oxidative stress in porcine oocyte maturation are still unclear. Here, we investigated the effects of asiatic acid on porcine oocyte in vitro maturation (IVM) and subsequent embryonic development competence after parthenogenetic activation (PA) and in vitro fertilization (IVF). The results of the present research showed that 10 µM asiatic acid supplementation did not affect the expansion of cumulus cells or polar body extrusion of porcine oocytes, while asiatic acid application significantly increased the subsequent blastocyst formation rate and quality of porcine PA and IVF embryos. Hydrogen peroxide (H2O2) is a reactive oxygen species (ROS) that induces oxidative stress in porcine oocytes. As expected, asiatic acid supplementation not only decreased intracellular ROS levels but also attenuated H2O2-induced intracellular ROS generation. Further analysis revealed that asiatic acid supplementation enhanced intracellular glutathione production, mitochondrial membrane potential, and ATP generation at the end of IVM. In summary, our results reveal that asiatic acid supplementation exerts beneficial effects on porcine oocytes by regulating oxidative stress during the IVM process and could act as a potential antioxidant in porcine oocytes matured in vitro production systems.
Subject(s)
Hydrogen Peroxide , In Vitro Oocyte Maturation Techniques , Animals , Blastocyst , Dietary Supplements , Embryonic Development , Hydrogen Peroxide/metabolism , Hydrogen Peroxide/pharmacology , In Vitro Oocyte Maturation Techniques/veterinary , Oocytes/metabolism , Oxidative Stress , Pentacyclic Triterpenes , Reactive Oxygen Species/metabolism , SwineABSTRACT
OBJECTIVES: Xanthohumol (XAN) is a unique component of Humulus lupulus L. and is known for its diverse biological activities. In this study, we investigated whether Xanthohumol could ameliorate memory impairment of APP/PS1 mice, and explored its potential mechanism of action. METHODS: APP/PS1 mice were used for in vivo test and were treated with N-acetylcysteine and Xanthohumol for 2 months. Learning and memory levels were evaluated by the Morris water maze. Inflammatory and oxidative markers in serum and hippocampus and the deposition of Aß in the hippocampus were determined. Moreover, the expression of autophagy and apoptosis proteins was also evaluated by western blot. KEY FINDINGS: Xanthohumol significantly reduced the latency and increased the residence time of mice in the target quadrant. Additionally, Xanthohumol increased superoxide dismutase level and reduced Interleukin-6 and Interleukin-1ß levels both in serum and hippocampus. Xanthohumol also significantly reduced Aß deposition in the hippocampus and activated autophagy and anti-apoptotic signals. CONCLUSIONS: Xanthohumol effectively ameliorates memory impairment of APP/PS1 mice by activating mTOR/LC3 and Bax/Bcl-2 signalling pathways, which provides new insight into the neuroprotective effects of Xanthohumol.
Subject(s)
Amyloid beta-Peptides/metabolism , Flavonoids/pharmacology , Hippocampus/drug effects , Humulus/chemistry , Memory Disorders/metabolism , Propiophenones/pharmacology , TOR Serine-Threonine Kinases/metabolism , bcl-2-Associated X Protein/metabolism , Amyloid beta-Protein Precursor/metabolism , Animals , Apoptosis , Autophagy , Hippocampus/metabolism , Male , Maze Learning , Memory/drug effects , Memory Disorders/drug therapy , Mice, Transgenic , Microtubule-Associated Proteins/metabolism , Neuroinflammatory Diseases/drug therapy , Neuroinflammatory Diseases/metabolism , Neuroprotective Agents/pharmacology , Oxidative Stress/drug effects , Phytotherapy , Plant Extracts/pharmacology , Presenilin-1/metabolism , Signal TransductionABSTRACT
Glycine is a well-known free radical scavenger in the cellular antioxidant system that prevents oxidative damage and apoptosis. Excessive fluoride exposure is associated with multiple types of cellular damage in humans and animals. The objective of the present study was to investigate the protective effects of glycine on sodium fluoride (NaF) exposure and the possible underlying mechanisms in a porcine testicular Sertoli cell line model. Cellular viability and proliferation were examined following NaF exposure and glycine supplementation, and glycine dramatically ameliorated the decreases in NaF-induced porcine testicular Sertoli cell viability and proliferation. Further investigations revealed that glycine decreased NaF-induced intracellular reactive oxygen species production, DNA fragment accumulation and the apoptosis incidence in the porcine testicular Sertoli cell line; in addition, glycine improved mitochondrial function and ATP production. Notably, results of the SPiDER-ß-Gal analysis suggested that glycine alleviated NaF-induced cellular senescence and downregulated P53, P21, HMGA2 and P16INK4a gene expression in the porcine testicular Sertoli cell line. Collectively, the beneficial effects of glycine alleviate NaF-induced oxidative stress, apoptosis and senescence, and together with our previous findings, support the hypothesis that glycine plays an important role in protecting against NaF exposure-induced impairments in the porcine testicular Sertoli cell line.
Subject(s)
Aging/drug effects , Apoptosis/drug effects , Glycine/pharmacology , Sodium Fluoride/toxicity , Adenosine Triphosphate/metabolism , Animals , Cell Line , Cell Survival/drug effects , DNA Fragmentation/drug effects , Gene Expression Regulation , Male , Oxidative Stress/drug effects , Reactive Oxygen Species , Sertoli Cells/drug effects , SwineABSTRACT
ETHNOPHARMACOLOGICAL RELEVANCE: Piper sarmentosum Roxb. (Piperaceae) is a traditional medicinal plant widely distributed in India, Malaysia, Thailand, and the southeastern coastal areas of China including Fujian, Guangdong, and Guizhou. It has been used for centuries for the treatment of wind-cold cough, fever, rheumatism arthralgia, diarrhea dysentery, postpartum foot swelling, stomachache, toothache, diabetes, and traumatic injury. AIMS OF THE REVIEW: To critically anayze the literature for the botany, traditional uses, phytochemistry, pharmacology, toxicity, and clinical trials of P. sarmentosum in order to provide a scientific consensus for further research and discovery of potential candidate drugs. MATERIALS AND METHODS: The contents of this review were sourced from electronic databases including PubMed, SciFinder, Web of Science, Science Direct, Elsevier, Google Scholar, Chinese Knowledge On frastructure (CNKI), Wanfang, Chinese Scientific and Technological Periodical Database (VIP), Chinese Biomedical Database (CBM), Cochrane Controlled register of Clinical Trials, Clinical Trials. gov, and Chinese Clinical Trial Registry. Chinese medicine books published over the years were used to elucidate the traditional uses of P. sarmentosum and additional information was also collected from Yao Zhi website (https://db.yaozh.com/). RESULTS: Phytochemical analyses of the chemical constituents of P. sarmentosum include essential oil, alkaloids, flavonoids, lignans, and steroids. The literature supports the ethnomedicinal uses of P. sarmentosum for the treatment of cold, gastritis, and rheumatoid joint pain, and further confirms its relatively new pharmacological activities, including anti-inflammatory, antineoplastic, and antipyretic activities. Other biological roles such as anti-osteoporosis, antibacterial, antidepressant, anti-atherosclerotic, and hypoglycemic activities have also been reported. However, the methodologies employed in individual studies are limited. CONCLUSIONS: There is convincing evidence from both in vitro and in vivo studies supporting the traditional use of P. sarmentosum and it is imperative that natural bioactive compounds are examined further. More efforts should be focused on the pharmacodynamic constituents of P. sarmentosum to provide practical basis for quality control, and additional studies are needed to understand the mechanism of their action. Further studies on the comprehensive evaluation of medicinal quality and understandings of serum chemistry, multi-target network pharmacology, and molecular docking technology of P. sarmentosum are of great importance and should be considered.
Subject(s)
Drugs, Chinese Herbal/therapeutic use , Ethnobotany/methods , Ethnopharmacology/methods , Medicine, Chinese Traditional/methods , Phytochemicals/therapeutic use , Piper , Animals , Anti-Infective Agents/chemistry , Anti-Infective Agents/isolation & purification , Anti-Infective Agents/therapeutic use , Antineoplastic Agents, Phytogenic/chemistry , Antineoplastic Agents, Phytogenic/isolation & purification , Antineoplastic Agents, Phytogenic/therapeutic use , Drugs, Chinese Herbal/chemistry , Drugs, Chinese Herbal/isolation & purification , Ethnobotany/trends , Ethnopharmacology/trends , Humans , Medicine, Chinese Traditional/trends , Molecular Docking Simulation/methods , Phytochemicals/chemistry , Phytochemicals/isolation & purification , Phytotherapy/methods , Phytotherapy/trendsABSTRACT
ETHNOPHARMACOLOGICAL RELEVANCE: Osteoporosis and Alzheimer's disease (AD) are both senile diseases, which are closely related to oxidative stress. Bajitianwan (BJTW) is a classic Chinese formulation consisting of seven herbal drugs: the root of Morinda officinalis F.C.How., root and rhizome of Acorus tatarinowii Schott, the root bark of Lycium chinense Mill., the sclerotium of Poria cocos (Schw.) Wolf, the root of Polygala tenuifolia Willd., sclerotium with host wood of Poria cocos (Schw.) Wolf and root and rhizome of Panax ginseng C. A. Mey. BJTW has been used for the treatment of osteoporosis and AD for hundreds of years. AIM OF THE STUDY: This study aimed to investigate the protective effects of BJTW in the amelioration of memory impairment and bone loss induced by D-galactose and to explore the underlying mechanism. MATERIALS AND METHODS: The aging model was established in male Wistar rats by subcutaneous injection of D-galactose (100 mg/kg), and the rats were treated with huperzine-A, alendronate sodium, or the aqueous extract of BJTW for 4 months. Cognitive performance was evaluated with the Morris water maze. Rat femurs were scanned using microcomputed tomography to obtain three-dimensional imagery of bone microstructure. The impact of D-galactose on the expression of Forkhead box O1 and superoxide dismutase 2 in femur tissue was also evaluated. RESULTS: For the model group, BJTW treatment significantly reduced the latency time for finding the target platform in the directional swimming test and increased time spent swimming in the target quadrant with the probe test. Additionally, BJTW treatment alleviated D-galactose-induced bone loss through regulation of levels of alkaline phosphatase, osteocalcin, osteoprotegerin, and receptor activator of nuclear factor kappa B ligand. Furthermore, BJTW treatment increased catalase and glutathione peroxidase levels in serum, reduced malondialdehyde content in hippocampus, and upregulated expression of Forkhead O1, which upregulated superoxide dismutase 2 in the femur. CONCLUSIONS: BJTW had positive effects on age-related memory impairments and bone loss. It may be a promising antioxidant candidate for treatment of Alzheimer's disease and osteoporosis.
Subject(s)
Antioxidants/pharmacology , Behavior, Animal/drug effects , Bone Density Conservation Agents/pharmacology , Bone Remodeling/drug effects , Drugs, Chinese Herbal/pharmacology , Femur/drug effects , Hippocampus/drug effects , Maze Learning/drug effects , Memory Disorders/prevention & control , Nootropic Agents/pharmacology , Osteoporosis/prevention & control , Oxidative Stress/drug effects , Age Factors , Animals , Cognition/drug effects , Disease Models, Animal , Femur/metabolism , Femur/physiopathology , Galactose , Hippocampus/metabolism , Hippocampus/physiopathology , Male , Memory Disorders/chemically induced , Memory Disorders/metabolism , Memory Disorders/physiopathology , Osteoporosis/chemically induced , Osteoporosis/metabolism , Osteoporosis/physiopathology , Rats, WistarABSTRACT
BACKGROUND AND AIMS: This paper was primarily devoted to understand the interactions of soil aggregates, organic carbon (C) and carbon cycle enzymes in aggregates under different fertilization managements, aiming to identify the effects of organic and inorganic fertilizer amendments on soil organic C accumulation and the activities of carbon cycle enzymes within aggregates in Vertisol. METHODS: A Vertisol soil following 4-year compost and inorganic fertilizer amendments, i.e. no fertilizer (CK), mineral fertilizer (FR) and 60% compost N plus 40% fertilizer N (FRM), was collected to identify the dynamics of organic C, enzymes activities and their associations with macroaggregation using aggregate fractionation techniques. RESULTS: The organic C content in all FR and FRM treatments was 8.24-41.15% higher than that in CK. An increased amounts of carbon cycle enzymes in aggregates or 0-20 cm bulk soil were also observed in FRM plots. Compared to FR, FRM significantly strengthened the structural stability of macroaggregates and the intimate connection between enzyme activities and macroaggregates. CONCLUSIONS: As a recommended measure, supplementation with organic manure such as compost strengthened the process of mutual promotion between carbon cycle enzymes and macroaggregates, and the synergistic effect would be highly beneficial to soil organic C sequestration.
Subject(s)
Carbon Cycle , Composting , Fertilizers/analysis , Soil/chemistry , Agriculture/methods , Carbon/analysis , Carbon Cycle/physiology , Carbon Sequestration , China , Enzymes/analysis , Triticum/growth & development , Zea mays/growth & developmentABSTRACT
OBJECTIVE: An experiment was conducted to determine the effects of L-arginine (L-Arg) and N-carbamoylglutamic acid (NCG) on the growth, metabolism, immunity and community of cecal bacterial flora of weanling and young rabbits. METHODS: Eighteen normal-grade male weanling Japanese White Rabbits (JWR) were selected and randomly divided into 6 groups with or without L-Arg and NCG supplementation. The whole feeding process was divided into weanling stage (Day 37 to 65) and young stage (Day 66 to 85). The effects of L-Arg and NCG on the growth, metabolism, immunity and development of the ileum and jejunum were compared via nutrient metabolism experiments and histological assessment. The different communities of cecal bacterial flora affected by L-Arg and NCG were assessed using high-throughput sequencing technology and bioinformatics analysis. RESULTS: The addition of L-Arg and NCG were able to enhance the growth of weanling and young rabbit by increasing the nitrogen metabolism, protein efficiency ratio, and biological value, as well as feed intake, daily weight gain. Both L-Arg and NCG were able to increase the concentration of IgA, IgM, and IgG. NCG was superior to L-Arg in promoting intestinal villus development by increasing villus height and V/C index, reducing the crypt depth. The effects of L-Arg and NCG on the cecal bacterial flora were mainly concentrated in different genera, including Parabacteroides, Roseburia, dgA-11_gut_group, Alistipes, Bacteroides, and Ruminococcaceae_UCG-005. These bacteria function mainly in amino acid transport and metabolism, energy production and conversion, lipid transport and metabolism, recombination and repair, cell cycle control, cell division, and cell motility. CONCLUSION: L-Arg and NCG have promotional ability on the growth and immunity of weanling and young Japanese White Rabbits, as well as their effects on the jejunum and ileum villi. L-Arg and NCG have different effects in the promotion of nutrient utilization, relieving inflammation and enhancing adaptability through regulating microbial community.
ABSTRACT
Zinc(II) complexes of curcumin display moderate cytotoxicity towards cancer cells at low micromolar concentrations. However, the clinical use of zinc(II) complexes is hampered by hydrolytic insolubility and poor bioavailability and their anticancer mechanisms remain unclear. Here, we investigated the efficacy and mechanism of action of a polyvinylpyrrolidone (PVP-k30)-based solid dispersion of Zn(II)-curcumin (ZnCM-SD) against hepatocellular carcinoma (HCC) in vitro and in vivo. In vitro assays revealed ZnCM-SD not only reduced the viability of HepG2 cells and SK-HEP1 cells in a dose-dependent manner, but also potently and synergistically enhanced cell growth inhibition and cell death in response to doxorubicin by regulating cellular zinc homeostasis. ZnCM-SD was internalized into the cells via non-specific endocytosis and degraded to release curcumin and Zn2+ ions within cells. The anticancer effects also occur in vivo in animals following the oral administration of ZnCM-SD, without significantly affecting the weight of the animals. Interestingly, ZnCM-SD did not reduce tumor growth or affect zinc homeostasis in HepG2-bearing mice after gut microbiome depletion. Moreover, administration of ZnCM-SD alone or in combination with doxorubicin significantly attenuated gut dysbiosis and zinc dyshomeostasis in a rat HCC model. Notably, fecal microbiota transplantation revealed the ability of ZnCM-SD to regulate zinc homeostasis and act as a chemosensitizer for doxorubicin were dependent on the gut microbiota. The crucial role of the gut microbiota in the chemosensitizing ability of ZnCM-SD was confirmed by broad-spectrum antibiotic treatment. Collectively, ZnCM-SD could represent a simple, well-tolerated, safe, effective therapy and function as a novel chemosensitizing agent for cancer.
Subject(s)
Antineoplastic Agents/therapeutic use , Carcinoma, Hepatocellular/drug therapy , Curcumin/therapeutic use , Doxorubicin/therapeutic use , Gastrointestinal Microbiome/drug effects , Liver Neoplasms/drug therapy , Zinc/therapeutic use , Animals , Antineoplastic Agents/chemistry , Antineoplastic Agents/pharmacology , Carcinoma, Hepatocellular/blood , Carcinoma, Hepatocellular/microbiology , Carcinoma, Hepatocellular/pathology , Cell Line, Tumor , Cell Survival/drug effects , Curcumin/chemistry , Curcumin/pharmacology , Doxorubicin/chemistry , Doxorubicin/pharmacology , Drug Synergism , Fecal Microbiota Transplantation , Female , Gastrointestinal Microbiome/genetics , Homeostasis/drug effects , Humans , Ileum/drug effects , Ileum/pathology , Liver/drug effects , Liver/pathology , Liver Neoplasms/blood , Liver Neoplasms/microbiology , Liver Neoplasms/pathology , Male , Mice, Inbred BALB C , RNA, Ribosomal, 16S/analysis , Rats, Sprague-Dawley , Zinc/blood , Zinc/chemistry , Zinc/pharmacologyABSTRACT
Reducing the applications of mineral phosphorus (P) fertilizers and supplementing them by organic fertilizers is becoming a necessary practice in the North China Plain due to overuse of mineral P fertilizers and improper disposal of organic wastes. Knowledge is needed about how the long-term substitution of mineral fertilizers by organic fertilizers affects soil P forms in order to understand soil P transformation and crop P uptake. In this study, we used solution 31P nuclear magnetic resonance (NMR) spectroscopy to characterize P forms in fluvo-aquic soil after 26â¯years of different fertilization management strategies, organic compost (OM), half compost in combination with half mineral fertilizer NPK (1/2 OM), mineral fertilizer NPK (NPK), mineral fertilizer NK (NK), and an unfertilized control (CK). Results showed that the P extraction efficiency using NaOH-EDTA varied from 13.0 to 27.7% for the soils of the treatments. 31P NMR spectra indicated that the majority of P was in the form of orthophosphate for all the treatments, which constituted 64.3-83.5% of the total extracted P. The application of P fertilizers significantly increased the concentrations of orthophosphate, monoesters and diesters regardless of the P fertilization method, although the proportions of monoesters and diesters were higher in CK. The proportions and concentrations of orthophosphate significantly decreased when all mineral fertilizers were replaced by compost. There was no significant difference in the proportions and concentrations of total organic P, corrected monoesters and diesters in NaOH-EDTA extracts of soils among NPK, 1/2OM and OM treatments. Decreasing mineral P fertilizers and partly replacing them by organic fertilizer in fluvo-aquic soil might increase soil test (Olsen) P and crop P uptake through the degradation of applied organic P forms.
ABSTRACT
The leaves of Aster glehni Fr. Schm. (Asteraceae) have been used to treat insomnia in Korea. Insomnia is a common adverse effect of therapeutic agents for Alzheimer's disease (AD), and the control of sleep disturbance may prevent dementia. We hypothesized that the leaves of A. glehni can attenuate cognitive dysfunctions observed in AD. We observed the ameliorating effects of the ethanolic extract of leaves of A. glehni (AG-D) on memory dysfunction through the Morris water maze test, the passive avoidance test, and the Y-maze test. We performed acetylcholinesterase (AChE) activity assay and Western blotting to determine the mechanism of action of AG-D. AG-D significantly attenuated memory dysfunction observed in the above behavior studies and inhibited the activity of AChE. AG-D also increased the levels of phosphorylation extracellular signal-regulated kinase (ERK), cAMP response element-binding protein (CREB), phosphatidylinositol 3-kinase (PI3K), protein kinase B (Akt), and glycogen synthase kinase 3ß (GSK-3ß) and the expression levels of brain-derived neurotrophic factor (BDNF) in the hippocampi. These results suggest that AG-D ameliorates memory impairments by AChE inhibition and activation of ERK-CREB-BDNF and PI3K-Akt-GSK-3ß signaling pathways. Taken together, this study suggests that AG-D could be used as a potential treatment for cognitive dysfunction.
Subject(s)
Aster Plant/chemistry , Cognitive Dysfunction/drug therapy , Plant Extracts/administration & dosage , Acetylcholinesterase/genetics , Acetylcholinesterase/metabolism , Animals , Cognitive Dysfunction/chemically induced , Cognitive Dysfunction/metabolism , Cognitive Dysfunction/psychology , Cyclic AMP Response Element-Binding Protein/genetics , Cyclic AMP Response Element-Binding Protein/metabolism , Hippocampus/drug effects , Hippocampus/metabolism , Humans , Male , Maze Learning , Memory/drug effects , Mice , Phosphatidylinositol 3-Kinases/genetics , Phosphatidylinositol 3-Kinases/metabolism , Scopolamine/adverse effects , Signal Transduction/drug effectsABSTRACT
Unbalanced fertilization lacking nitrogen (N), phosphorus (P), or potassium (K) is a worldwide phenomenon; however, whether they affect bacterial community composition and intraspecific interactions in a similar pattern and how they affect bacterial activity are not systematically compared. Soils under different kinds of unbalanced fertilization in a 21-year field experiment were collected to investigate the variation in dehydrogenase activity (DHA), bacterial community diversity, structure, composition, and possible interactions. Compared to the balanced fertilization of NPK, the DHA from unbalanced fertilization of NP, PK, and NK was 8.70, 11.59, and 14.17% lower, respectively, and from the unfertilized treatment (Nil) was 13.41% lower; however, the Shannon index from NP, PK, and Nil was 4.48-7.21% higher and from NK was 3.95% lower. Based on principal coordinate analyses (PCoA), bacterial community structure was separated by N application or not along PCo1 and was further separated by P application or not along PCo2, indicating a more influence by N deficiency. Moreover, the structure was mainly determined by soil pH, soil organic carbon (SOC), and total phosphorus (TP). The network complexity using co-occurrence analysis followed the order NP > NPK > PK > NK > Nil, indicating a more influence by P deficiency on intraspecific interactions. Structural equation modeling (SEM) revealed that the reduced DHA in NP was mainly regulated by the decreased SOC and increased Shannon index, in PK by the decreased SOC and increased Shannon index and pH, and in NK by the decreased SOC and TP and increased PCo2. The significantly lower abundance of Bacteroidetes and Chitinophagaceae in NK may also contribute to the reduced DHA. Our results imply that N deficiency had the greatest impact on bacterial community structure and composition, P deficiency had the greatest impact on network construction and bacterial activity, and K deficiency has minimal effect. Our results also suggest that main factors regulating the variation in soil functions may vary among different nutrient deficiencies.
Subject(s)
Fertilizers , Nitrogen , Phosphorus , Potassium , Soil Microbiology , Bacteria/metabolism , Bacteroidaceae/metabolism , China , Fertilizers/analysis , Hydrogen-Ion Concentration , Oxidoreductases/metabolism , Soil/chemistryABSTRACT
Bee pollen consists of floral pollen mixed with bee secretions and nectar. It has been considered as a functional food and has different kinds of biologically active ingredients, such as flavonoids, polyphenols, phytosterols and minerals. However, its function in cognition has yet been investigated. In the present study, we investigated the ameliorating effect of bee pollen against scopolamine-caused cognitive impairment through the passive avoidance test, the Y-maze test and the Morris water maze test. In addition, Western blotting was employed to verify the effects of bee pollen on memory-related signaling molecules in the hippocampus. Bee pollen extract (100 or 300 mg/kg, per os (p.o.)) obviously reversed scopolamine-caused cognitive impairment in the passive avoidance test, ameliorated spontaneous alternation versus the scopolamine-treated group in the Y-maze test and prolonged swimming time in the target zone in the Morris water maze test. In addition, the phosphorylation levels of extracellular signal-regulated kinase (ERK), cAMP response element-binding protein (CREB), protein kinase B (Akt) and glycogen synthase kinase-3ß (GSK-3ß), and the expression levels of brain-derived neurotrophic factor (BDNF) and tissue plasminogen activator (tPA) in the hippocampi, were increased in response to the treatment with bee pollen extract (100 or 300 mg/kg, p.o.). These results indicated that bee pollen ameliorates cognitive impairment induced by cholinergic blockade through the enhancing conversion of proBDNF to mature BDNF by tPA, probably, through the ERK-CREB pathway or Akt-GSK-3ß signaling pathway and would be a useful agent for the treatment of cognitive dysfunction.