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1.
J Ethnopharmacol ; 328: 118113, 2024 Jun 28.
Article in English | MEDLINE | ID: mdl-38548119

ABSTRACT

ETHNOPHARMACOLOGICAL RELEVANCE: Alzheimer's disease (AD) is a progressive neurodegenerative disease. Tianma-Gouteng Pair (TGP), commonly prescribed as a pair-herbs, can be found in many Chinese medicine formulae to treat brain diseases. However, the neuroprotective effects and molecular mechanisms of TGP remained unexplored. AIM OF THE STUDY: This study investigated the difference between the TgCRND8 and 5 × FAD transgenic mice, the anti-AD effects of TGP, and underlying molecular mechanisms of TGP against AD through the two mouse models. METHODS: Briefly, three-month-old TgCRND8 and 5 × FAD mice were orally administered with TGP for 4 and 6 months, respectively. Behavioral tests were carried out to determine the neuropsychological functions. Moreover, immunofluorescence and western blotting assays were undertaken to reveal the molecular mechanisms of TGP. RESULTS: Although TgCRND8 and 5 × FAD mice had different beta-amyloid (Aß) burdens, neuroinflammation status, and cognition impairments, TGP exerted neuroprotective effects against AD in the two models. In detail, behavioral tests revealed that TGP treatment markedly ameliorated the anxiety-like behavior, attenuated the recognition memory deficits, and increased the spatial learning ability as well as the reference memory of TgCRND8 and 5 × FAD mice. Moreover, TGP treatment could regulate the beta-amyloid precursor protein (APP) processing by inhibiting the Aß production enzymes such as ß- and γ-secretases and activating Aß degrading enzyme to reduce Aß accumulation. In addition, TGP reduced the Aß42 level, the ratio of Aß42/Αß40, Aß accumulation, and tau hyperphosphorylation in both the 5 × FAD and TgCRND8 mouse models. Furthermore, TGP ameliorated neuroinflammation by decreasing the densities of activated microglia and astrocytes, and inhibiting the production of inflammatory cytokines. TGP upregulated the SIRT1 and AMPK, and downregulated sterol response element binding protein 2 (SREBP2) in the brain of TgCRND8 mice and deactivation of the EPhA4 and c-Abl in the brain tissues of 5 × FAD mice. CONCLUSION: Our experiments for the first time revealed the neuroprotective effects and molecular mechanism of TGP on 5 × FAD and TgCRND8 transgenic mouse models of different AD stages. TGP decreased the level of Aß aggregates, improved the tauopathy, and reduced the neuroinflammation by regulation of the SIRT1/AMPK/SREBP2 axis and deactivation of EPhA4/c-Abl signaling pathway in the brains of TgCRND8 and 5 × FAD mice, respectively. All these findings unequivocally confirmed that the TGP would be promising in developing into an anti-AD therapeutic pharmaceutical.


Subject(s)
Alzheimer Disease , Neurodegenerative Diseases , Neuroprotective Agents , Mice , Animals , Alzheimer Disease/drug therapy , Alzheimer Disease/metabolism , Mice, Transgenic , Sirtuin 1 , Neuroprotective Agents/pharmacology , Neuroprotective Agents/therapeutic use , Neuroinflammatory Diseases , AMP-Activated Protein Kinases , Amyloid beta-Peptides/metabolism , Amyloid beta-Protein Precursor/metabolism , Cognition , Disease Models, Animal
2.
Medicine (Baltimore) ; 103(7): e36593, 2024 Feb 16.
Article in English | MEDLINE | ID: mdl-38363942

ABSTRACT

Doxorubicin (DOX) is one of the most effective chemotherapeutic agents. However, the nonselective effect leads to serious cardiotoxicity risk in clinical use. Curcumin is a well-known dietary polyphenol that showed a protective effect against the cardiotoxic effect of DOX. This study aimed to assess the role of curcumin in protection against DOX-induced cardiotoxicity. Potential compound and disease targets were obtained from relevant databases, and common targets were screened. Protein-protein interaction (PPI) was used to predict the core targets. Gene ontology (GO) bioprocess analysis and Kyoto encyclopedia of genes and genome enrichment analysis enriched the possible biological processes (BP), cellular components, molecular function, and signaling pathways involved. Finally, the binding of curcumin to target proteins was evaluated through molecular docking. The docking score verified the reliability of the prediction results. In total, 205 curcumin and 700 disease targets were identified. A topological analysis of the PPI network revealed 10 core targets including TP53, tumor necrosis factor-alpha (TNF), AKT1, vascular endothelial growth factor A (VEGFA), prostaglandin-endoperoxide synthase 2 (PTGS2), signal transducer and activator of the transcription 3 (STAT3), HIF1A, MYC, epidermal growth factor receptor (EGFR), and CASP3 (Caspase-3). Furthermore, the enrichment analyses indicated that the effects of curcumin were mediated by genes related to oxidation, inflammation, toxification, cell proliferation, migration, apoptosis, wounding, metabolism, proteolysis, and the signaling pathway of calcium (Ca2+). Molecular docking showed that curcumin could bind with the target proteins with strong molecular force, exhibiting good docking activity. Curcumin has a multi-cardioprotective effect by modulating the core targets' expression in DOX-induced cardiotoxicity. This study elucidated the key target proteins and provided a theoretical basis for further exploring curcumin in the prevention and treatment of DOX-induced cardiotoxicity.


Subject(s)
Curcumin , Drugs, Chinese Herbal , Humans , Molecular Docking Simulation , Curcumin/pharmacology , Curcumin/therapeutic use , Vascular Endothelial Growth Factor A , Network Pharmacology , Cardiotoxicity/drug therapy , Cardiotoxicity/etiology , Cardiotoxicity/prevention & control , Reproducibility of Results
3.
J Environ Manage ; 347: 119076, 2023 Dec 01.
Article in English | MEDLINE | ID: mdl-37748299

ABSTRACT

Excessive phosphorus (P) in surface water can lead to serious eutrophication and economic losses. Iron-based constructed wetland (CW) is considered as a promising solution to eliminate P effectively due to the advantage of low-cost. However, there is limited available information on the microbial removal mechanism of P in iron-based CW up to now. Therefore, CW with iron scrap was constructed to investigate the treatment performance and microbial removal mechanism in this study. Results showed that efficient and stable P removal (97.09 ± 1.90%) was achieved in iron scrap-based CW during the experiment period, which was attributed to the precipitation of iron and P and improved microbially mediated P removal. Metagenomic analysis showed that microbial diversity was enhanced and phosphate accumulating organisms (e.g., Dechloromonas and Tetrasphaera) were enriched in CW with iron scrap, which explained higher P removal reasonably. In addition, the abundance of genes involved in the P starvation (e.g., phoB), uptake and transport (e.g., pstB) were enhanced in iron scrap-based CW. Enrichment analysis demonstrated that phosphotransferase pathway was also significantly up-regulated in CW with iron scraps, indicating that the energy supply of microbial P removal was enhanced. These findings provide a better understanding of the microbial removal mechanism of P in iron-based CW.


Subject(s)
Bioelectric Energy Sources , Wastewater , Wetlands , Iron , Phosphorus
4.
J Environ Manage ; 345: 118840, 2023 Nov 01.
Article in English | MEDLINE | ID: mdl-37604105

ABSTRACT

Phosphorus (P) recovery from wastewaters treated with constructed wetlands (CWs) could alleviate the current global P crisis but has not received sufficient attention. In this study, P transformation in different magnesium-based electrochemical CWs, including micro-electrolysis CW (M-CW), primary battery CW (P-CW), and electrolysis CW (E-CW), was thoroughly examined. The results revealed that the P removal efficiency was 53.0%, 75.8%, and 61.9% in the M-CW, E-CW, and P-CW, respectively. P mass balance analysis showed that P electrode deposition was the main reason for the higher P removal in the E-CW and P-CW. Significant differences were found between the E-CW and P-CW, P was distributed primarily on the magnesium plate in the P-CW but was distributed on the carbon plate in the E-CW. The E-CW had excellent P recovery capacity, and struvite was the major P recovery product. More intense magnesium plate corrosion and alkaline environment increased struvite precipitation in the E-CW, with the proportion of 61.6%. The results of functional microbial community analysis revealed that the abundance of electroactive bacteria was positively correlated with the deposition of struvite. This study provided an essential reference for the targeted electrochemical regulation of electric field processes and microorganisms in CWs to enhance P recovery.


Subject(s)
Waste Disposal, Fluid , Wastewater , Waste Disposal, Fluid/methods , Magnesium , Phosphorus/analysis , Struvite , Wetlands , Nitrogen/analysis
5.
J Hazard Mater ; 455: 131633, 2023 08 05.
Article in English | MEDLINE | ID: mdl-37196443

ABSTRACT

Struvite production can recover ammonia and phosphorous from digested wastewater as fertilizer. During struvite generation, most of the heavy metals was co-precipitated with ammonia and phosphorous into struvite. Understanding the precipitation behavior of heavy metals with suspended solids (SS) might provide the possible strategy for the control of co-precipitation. In this study, the distribution of heavy metals in SS and their role on the co-precipitation during struvite recovery from digested swine wastewater were investigated. The results showed that the concentration of heavy metal (including Mn, Zn, Cu, Ni, Cr, Pb and As) ranged from 0.05 to 17.05 mg/L in the digested swine wastewater. The distribution analysis showed that SS with particles > 50 µm harbored most of individual heavy metal (41.3-55.6%), followed by particles 0.45-50 µm (20.9-43.3%), and SS-removed filtrate (5.2-32.9%). During struvite generation, 56.9-80.3% of individual heavy metal was co-precipitated into struvite. The contributions of SS with particles > 50 µm, 0.45-50 µm, and SS-removed filtrate on the individual heavy metal co-precipitation were 40.9-64.3%, 25.3-48.3% and 1.9-22.9%, respectively. These finding provides potential way for controlling the co-precipitation of heavy metals in struvite.


Subject(s)
Metals, Heavy , Wastewater , Animals , Swine , Struvite , Waste Disposal, Fluid/methods , Ammonia/analysis , Metals, Heavy/analysis , Phosphorus , Phosphates/analysis
6.
Chemosphere ; 313: 137429, 2023 Feb.
Article in English | MEDLINE | ID: mdl-36462565

ABSTRACT

Substrate clogging is one of the major operation challenges of subsurface flow constructed wetlands (SSF-CWs). And the phosphorus (P) removal performance and stability of P accumulation of SSF-CWs would be varied with the development of substrate clogging. In this study, three horizontal SSF-CWs microcosms with different clogging degrees were conducted to explore the mechanism of P accumulation behavior influenced by substrate clogging. Increase in clogging degree resulted in hydraulic retention time (HRT) diminution and adsorption sites increase, which jointly led to reduced P removal efficiency at low clogging degree (L-CW), however, higher P removal efficiency was obtained as adsorption sites increase offset HRT diminution at high clogging degree (H-CW). Substrate adsorption was the primary removal pathway in all SSF-CW systems. It accounted for 77.86 ± 2.63% of the P input in the H-CW, significantly higher than the control (60.08 ± 4.79%). This was attributed to a higher proportion of Fe/Al-P accumulated on the substrate of H-CW, since clogging aggravated the anaerobic condition and promoted the generation of Fe ions. The increase in clogging degree also elevated the release risk of the accrued P in SSF-CWs, since Fe/Al-P was considered bioavailable and readily released under environmental disturbance. The obtained results provide new insights into the P transport and transformation in SSF-CWs and would be helpful to optimize substrate clogging management.


Subject(s)
Waste Disposal, Fluid , Wetlands , Waste Disposal, Fluid/methods , Phosphorus/metabolism
7.
PeerJ ; 10: e14602, 2022.
Article in English | MEDLINE | ID: mdl-36570011

ABSTRACT

Soil salinity has been an increasing problem worldwide endangering crop production and human food security. It is an ideal strategy to excavate stress resistant genes and develop salt tolerant crops. NAC (no apical meristem/Arabidopsis transcription activation factor/cup-shaped cotyledon) transcription factors have been demonstrated to be involved in salt stress response. However, relevant studies have not been observed in garlic, an important vegetable consumed in the world. In this study, a total of 46 AsNAC genes encoding NAC proteins were identified in garlic plant by transcriptome data. Phylogenetic analysis showed that the examined AsNAC proteins were clustered into 14 subgroups. Motif discovery revealed that the conserved domain region was mainly composed of five conserved subdomains. Most of the genes selected could be induced by salt stress in different tissues, indicating a potential role in salt stress response. Further studies may focus on the molecular mechanisms of the AsNAC genes in salt stress response. The results of the current work provided valuable resources for researchers aimed at developing salt tolerant crops.


Subject(s)
Arabidopsis , Garlic , Humans , Transcription Factors/genetics , Transcriptome , Arabidopsis/genetics , Garlic/genetics , Transcriptional Activation , Meristem/genetics , Phylogeny , Cotyledon/genetics , Plant Proteins/genetics , Gene Expression Regulation, Plant , Salt Stress/genetics
8.
Phytomedicine ; 106: 154441, 2022 Nov.
Article in English | MEDLINE | ID: mdl-36108371

ABSTRACT

BACKGROUND: Alzheimer's disease (AD) is one of the most prevalent neurodegenerative diseases. Patchouli alcohol (PA), a major active ingredient isolated from Pogostemonis Herba, exhibits extensive bioactivity in the central nervous system (CNS) and exerts neuroprotective effects. PURPOSE: This study aimed to investigate the anti-AD effects of PA in an animal model of AD and to elucidate the underlying molecular mechanisms. METHODS: The gas chromatography (GC) was used to determine the ability of PA to pass the blood-brain barrier (BBB) in rats after oral administration. The sporadic AD rat model was established by intracerebroventricularly (ICV) injection with streptozotocin (STZ). PA (25 and 50 mg/kg) was given to rat orally once daily for 42 consecutive days. Morris water maze (MWM) test was performed to determine the learning and memory functions of the STZ-induced AD rats. EX527, a silent information regulator 1 (SIRT1) selective inhibitor, was used to investigate the involvement of SIRT1 in the anti-AD effects of PA in rats. RESULTS: PA could penetrate the BBB. MWM test results showed that PA could significantly ameliorate the learning and memory deficits induced by STZ in rats. Meanwhile, PA enhanced the expression of SIRT1, and markedly alleviated the tau pathology by inhibiting the hyperacetylation (at the site of Lys174) and hyperphosphorylation (at the sites of Thr181, Thr205, Ser396 and Ser404) of tau protein. PA also efficiently suppressed the activation of microglia and astrocytes, and the beta-amyloid (Aß) expression and the deacetylation of nuclear factor-kappa B (NF-κB) at Lys 310 (K310) in the STZ-treated AD rats. EX527, a SIRT1 selective inhibitor, could partially abolish the cognitive deficits improving effect of PA and inhibit the down-regulation of acetylated tau and acetylated NF-κB p65, suggesting that PA exhibited neuroprotective effects against AD via upregulating SIRT1. CONCLUSION: This study reported for the first time that PA could penetrate the BBB to exert its protective effects on the brain after a single-dose oral administration. The current experimental findings also amply demonstrated that PA could improve the cognitive and memory impairments in the STZ-induced AD rat model. The underlying mechanisms involve the alleviations of neuroinflammation, tau pathology and Aß deposition via modulating of SIRT1 and NF-κB pathways. All these findings strongly suggest that PA is a promising naturally occurring compound worthy of further development into an anti-AD pharmaceutical.


Subject(s)
Alzheimer Disease , Neuroprotective Agents , Alzheimer Disease/metabolism , Animals , Disease Models, Animal , Hippocampus , Maze Learning , Memory Disorders/metabolism , NF-kappa B/metabolism , Neuroprotective Agents/pharmacology , Neuroprotective Agents/therapeutic use , Pharmaceutical Preparations/metabolism , Rats , Sesquiterpenes , Sirtuin 1/metabolism , Streptozocin/adverse effects , tau Proteins/metabolism
9.
Chemosphere ; 307(Pt 2): 135821, 2022 Nov.
Article in English | MEDLINE | ID: mdl-35944687

ABSTRACT

The polycyclic aromatic hydrocarbons (PAHs) are substantial wastewater pollutants emitted mostly by petroleum refineries and petrochemical industries, and their environmental fate has been of increasing concern among the public. Consequently, subsurface flow constructed wetlands (SFCWs) filled with Mn oxides (W-CW) or without Mn oxides (K-CW) were established to investigate the performance and mechanisms of pyrene (PYR) removal. The average removal rates of PYR in W-CW and K-CW were 96.00% and 92.33%, respectively. The PYR removal via other pathways (microbial degradation, photolysis, volatilisation, etc.) occupied a sizeable proportion, while the total PYR content in K-CW plant roots was significantly higher than that of W-CW. The microorganisms on the root surface and rhizosphere played an important role in PYR degradation in W-CW and K-CW and were higher in W-CW than that in K-CW in all matrix zones. The microorganisms between the 10-16 cm zone from the bottom of W-CW filled with Mn oxides (W-16) were positively correlated with PYR-degrading microorganisms, aerobic bacteria and facultative anaerobes, whereas K-16 without birnessite-coated sand was negatively correlated with these microorganisms.


Subject(s)
Environmental Pollutants , Petroleum , Polycyclic Aromatic Hydrocarbons , Oxides , Polycyclic Aromatic Hydrocarbons/metabolism , Pyrenes/metabolism , Sand , Wastewater , Wetlands
10.
Phytomedicine ; 104: 154346, 2022 Sep.
Article in English | MEDLINE | ID: mdl-35872445

ABSTRACT

BACKGROUND: Huang-Lian-Jie-Du Decoction is a traditional Chinese medicine formula which has long been used to treat inflammatory skin disease including AD. However, Gardeniae Fructus, a component herb of HLJDD, has noticeable toxicity in liver and kidney. We therefore replaced Gardeniae Fructus with Dictamni Cortex with a hope to derive at a modified HLJDD (MHLJDD) with better safety profile. PURPOSE: The present study aimed to develop MHLJDD and identify its active fraction as innovative therapeutic agents for AD using 2,4-dinitrobenzene (DNCB) and calcipotriol (MC903)-sensitized mouse models of AD. METHODS: MHLJDD and the combination of the 1-butanol-soluble-fraction and the water-soluble-fraction (MHLJDD-F) were given intragastrically to the DNCB-induced mice and MC903-induced mice for two weeks. The body weight, dorsal skin/ear thickness and severity of AD symptoms of the mice were measured throughout the study. Scratching behaviors were observed after drug treatment. The blood and dorsal skin/ear tissues of mice were harvested for histopathological examination and biochemical analyses. RESULTS: The results revealed that DNCB- and MC903-induced AD symptoms, including skin thickening, dryness, erythema and excoriations, in the dorsal skin and ears were significantly alleviated in the MHLJDD and MHLJDD-F-treated mice. Ceramides content and protein expressions of filaggrin and loricrin were also up-regulated after treatment with MHLJDD and MHLJDD-F. In addition, skin inflammation induced by DNCB and MC903 were markedly suppressed in the MHLJDD and MHLJDD-F-treated mice, and the action mechanisms involve suppression of the release of inflammatory cytokines, as well as downregulation of the activation of NF-κB and MAPKs pathways. Besides, MHLJDD and MHLJDD-F could reverse the abundance of gut microbiota induced by DNCB in mice. CONCLUSIONS: MHLJDD and MHLJDD-F could markedly relieve AD-like symptoms induced by DNCB and MC903 in mice through, at least in part, improving the epidermal barrier function and inhibiting skin inflammation via suppressing the activation of NF-κB and MAPKs pathways and regulation of the gut microflora dysbiosis. This study reported for the first time that MHLJDD and its active fraction could be used as innovative therapeutic agents for AD.


Subject(s)
Dermatitis, Atopic , NF-kappa B , Animals , Coptis chinensis , Cytokines/metabolism , Dermatitis, Atopic/chemically induced , Dermatitis, Atopic/drug therapy , Dermatitis, Atopic/metabolism , Dinitrobenzenes , Dinitrochlorobenzene , Disease Models, Animal , Inflammation/drug therapy , Mice , Mice, Inbred BALB C , NF-kappa B/metabolism , Skin/metabolism
11.
Front Surg ; 9: 896526, 2022.
Article in English | MEDLINE | ID: mdl-35599796

ABSTRACT

Purpose: To explore the application value of salvage autologous blood transfusion for massive hemorrhage occurring during ectopic pregnancy. Methods: A retrospective analysis was performed on the basis of the clinical data of patients in our hospital for the period January 2019 to December 2021. These patients were confirmed to have suffered massive hemorrhage from an ectopic pregnancy during surgery and were treated with blood transfusion. The patients were divided according to their blood transfusion method into three groups: an autologous group (n = 46) treated with salvage autologous blood transfusion, a mixed group (n = 28) treated with salvage autologous + allogeneic blood transfusion, and an allogeneic group (n = 41) treated with allogeneic blood transfusion. The volume of intra-abdominal bleeding, the volume of autologous and allogeneic blood transfusion, postoperative fever and blood transfusion reaction, hemodynamic indices [systolic blood pressure (SBP), diastolic blood pressure (DBP), oxygen saturation (SpO2), and heart rate (HR)] before and after blood transfusion; 24-h postoperative blood routine [hematocrit (HCT), hemoglobin (Hb), platelets (PLT), red blood cells (RBCs)], and electrolyte indices (Na+, K+, Cl-) were all compared among the three groups. Results: It was found that intra-abdominal bleeding volume in the autologous and mixed groups was higher than that in the allogeneic group (p < 0.05), and there was no statistical difference between the autologous and the mixed groups (p > 0.05). Autologous blood transfusion volume in the autologous group was higher than that in the mixed group (p < 0.05). Allogeneic blood transfusion volume in the allogeneic group was higher than that in the mixed group (p < 0.05). After blood transfusion treatment, the postoperative fever rates were 4.35%, 10.71%, and 19.51% in the autologous, mixed, and allogeneic groups, respectively, and the blood transfusion reaction rates were 0.00%, 3.57%, and 9.76%, respectively, which were lower in the autologous group than in the allogeneic group (p < 0.05). At 30 min after blood transfusion, SBP, DBP, and SpO2 were higher in all three groups than before blood transfusion (p < 0.05), and HR was lower than before blood transfusion (p < 0.05), but there was no statistically significant difference between the groups at 30 min after blood transfusion (p > 0.05). At the 24- h postoperative period, no statistical difference was found when HCT, Hb, PLT, RBC, Na+, K+, and Cl- were compared among the three groups (p > 0.05). Conclusion: The use of salvage autologous blood transfusion for treating massive hemorrhage occurring during ectopic pregnancy is a safe and feasible method for rescuing patients with such condition because it can rapidly replenish the patient's blood volume and save blood resources without causing postoperative hemodynamic, blood routine, and electrolyte abnormalities.

12.
Water Res ; 210: 118009, 2022 Feb 15.
Article in English | MEDLINE | ID: mdl-34974341

ABSTRACT

The utilization of natural ores and/or mine waste as substrate in constructed wetlands (CWs) to enhance nutrient removal performance has been gaining high popularity recently. However, the knowledge regarding the long-term feasibility and key removal mechanisms, particularly the potential negative environmental effects of contaminants leached from mine waste is far insufficient. This study, for the first time, performed a critical assessment by using different CWs with three mine waste (coal gangue, iron ore and manganese ore) as substrates in a 385-day experiment treating wastewater with varying nutrient loadings. The results showed that the addition of mine waste in CWs increased removal of total phosphorus (TP) by 17-34%, and total nitrogen (TN) by 11-51%. The higher removal of TP is mainly attributed to the strong binding mechanism of phosphate with the oxides and hydroxides of Mn, Fe and/or Al, which are leached out of mine waste. Moreover, integration of mine waste in CWs also significantly stimulated biofilm establishment and enriched the relative abundance of key functional genes related to the nitrogen cycle, supporting the observed high-rate nitrogen removal. However, leaching of heavy metals (Fe, Mn, Cu and Cr) from the beded mine waste in the experimented CWs was monitored, which further influenced cytoplasmic enzymes and created oxidative stress damage to plants, resulting in a decline of nutrient uptake by plants.


Subject(s)
Waste Disposal, Fluid , Wetlands , Nutrients , Phosphorus , Wastewater
14.
Int J Biol Sci ; 17(11): 2811-2825, 2021.
Article in English | MEDLINE | ID: mdl-34345209

ABSTRACT

Chemotherapy plays an irreplaceable role in the treatment of GC, but currently available chemotherapeutic drugs are not ideal. The application of medicinal plants is an important direction for new drug discovery. Through drug screening of GC organoids, we determined that ailanthone has an anticancer effect on GC cells in vitro and in vivo. We also found that AIL can induce DNA damage and apoptosis in GC cells. Further transcriptome sequencing of PDX tissue indicated that AIL inhibited the expression of XRCC1, which plays an important role in DNA damage repair, and the results were also confirmed by western blotting. In addition, we found that AIL inhibited the expression of P23 and that inhibition of P23 decreased the expression of XRCC1, indicating that AIL can regulate XRCC1 via P23. The results of coimmunoprecipitation showed that AIL can inhibit the binding of P23 and XRCC1 to HSP90. These findings indicate that AIL can induce DNA damage and apoptosis in GC cells. Meanwhile, AIL can decrease XRCC1 activity by downregulating P23 expression to inhibit DNA damage repair. The present study sheds light on the potential application of new drugs isolated from natural medicinal plants for GC therapy.


Subject(s)
Apoptosis/drug effects , DNA Repair/drug effects , Pyridinolcarbamate/metabolism , Quassins/pharmacology , Stomach Neoplasms/drug therapy , Ailanthus/chemistry , Animals , Cell Line, Tumor , Cell Proliferation/drug effects , DNA Damage/drug effects , Down-Regulation , Drug Discovery , Female , Humans , Male , Mice , Mice, Inbred BALB C , Mice, Nude , Stomach Neoplasms/metabolism , X-ray Repair Cross Complementing Protein 1/metabolism , Xenograft Model Antitumor Assays
15.
Sci Rep ; 11(1): 14511, 2021 07 15.
Article in English | MEDLINE | ID: mdl-34267240

ABSTRACT

Sepsis survivors present long-term cognitive deficits. The present study was to investigate the effect of early administration of high-dose vitamin C on cognitive function in septic rats and explore its possible cerebral protective mechanism. Rat sepsis models were established by cecal ligation and puncture (CLP). Ten days after surgery, the Morris water maze test was performed to evaluate the behavior and cognitive function. Histopathologic changes in the hippocampus were evaluated by nissl staining. The inflammatory cytokines, activities of antioxidant enzymes (superoxide dismutase or SOD) and oxidative products (malondialdehyde or MDA) in the serum and hippocampus were tested 24 h after surgery. The activity of matrix metalloproteinase-9 (MMP-9) and expressions of nuclear factor erythroid 2-related factor 2 (Nrf2) and heme oxygenase-1(HO-1) in the hippocampus were measured 24 h after surgery. Compared with the sham group in the Morris water maze test, the escape latency of sepsis rats was significantly (P = 0.001) prolonged in the navigation test, whereas the frequency to cross the platform and the time spent in the target quadrant were significantly (P = 0.003) reduced. High-dose vitamin C significantly decreased the escape latency (P = 0.01), but increased the time spent in the target quadrant (P = 0.04) and the frequency to cross the platform (P = 0.19). In the CLP+ saline group, the pyramidal neurons were reduced and distributed sparsely and disorderly, the levels of inflammatory cytokines of tumor necrosis factor (TNF)-α, interleukin (IL)-6, and IL-10 in the serum and hippocampus were significantly increased (P = 0.000), the blood brain barrier (BBB) permeability in the hippocampus was significantly (P = 0.000) increased, the activities of SOD in the serum and hippocampus were significantly (P = 0.000 and P = 0.03, respectively) diminished while the levels of MDA in the serum and hippocampus were significantly (P = 0.007) increased. High-dose vitamin C mitigated hippocampus histopathologic changes, reduced systemic inflammation and neuroinflammation, attenuated BBB disruption, inhibited oxidative stress in brain tissue, and up-regulated the expression of nuclear and total Nrf2 and HO-1. High-dose vitamin C significantly (P < 0.05) decreased the levels of tumor necrosis factor- (TNF)-α, interleukin-6 (IL-6), MDA in the serum and hippocampus, and the activity of MMP-9 in the hippocampus, but significantly (P < 0.05) increased the levels of SOD, the anti-inflammatory cytokine (IL-10) in the serum and hippocampus, and nuclear and total Nrf2, and HO-1 in the hippocampus. In conclusion, high-dose vitamin C can improve cognition impairment in septic rats, and the possible protective mechanism may be related to inhibition of inflammatory factors, alleviation of oxidative stress, and activation of the Nrf2/HO-1 pathway.


Subject(s)
Ascorbic Acid/pharmacology , Cognitive Dysfunction/prevention & control , Sepsis/complications , Animals , Ascorbic Acid/administration & dosage , Blood-Brain Barrier/drug effects , Blood-Brain Barrier/physiology , Cognitive Dysfunction/etiology , Disease Models, Animal , Dose-Response Relationship, Drug , Heme Oxygenase (Decyclizing)/metabolism , Hippocampus/drug effects , Hippocampus/pathology , Inflammation/drug therapy , Male , NF-E2-Related Factor 2/metabolism , Oxidative Stress/drug effects , Protective Agents/administration & dosage , Protective Agents/pharmacology , Rats, Sprague-Dawley , Sepsis/drug therapy , Sepsis/etiology
16.
Ecotoxicol Environ Saf ; 221: 112451, 2021 Sep 15.
Article in English | MEDLINE | ID: mdl-34174737

ABSTRACT

Manganese oxides and iron oxides have been widely introduced in constructed wetlands (CWs) for sewage treatment due to their extensiveness in nature and their ability to participate in various reactions, but their effects on greenhouse gas (GHG) emissions remain unclear. Here, a set of vertical subsurface-flow CWs (Control, Fe-VSSCWs, and Mn-VSSCWs) was established to comprehensively evaluate which are the better metal substrate materials for CWs, iron oxides or manganese oxides, through water quality and the global warming potential (GWP) of nitrous oxide (N2O), methane (CH4), and carbon dioxide (CO2). The results revealed that the removal efficiencies of chemical oxygen demand (COD), total nitrogen (TN), and total phosphorus (TP) in Mn-VSSCWs were all higher than that in Fe-VSSCWs, and manganese oxides could almost completely suppress the CH4 production and reduce GWP (from 8.15 CO2-eq/m2/h to 7.17 mg CO2-eq/m2/h), however, iron oxides promoted GWP (from 8.15 CO2-eq/m2/h to 10.84 mg CO2-eq/m2/h), so manganese oxides are the better CW substrate materials to achieve effective sewage treatment while reducing the greenhouse gas effect.


Subject(s)
Air Pollutants/chemistry , Ferric Compounds/chemistry , Greenhouse Effect/prevention & control , Manganese Compounds/chemistry , Oxides/chemistry , Water Purification/methods , Wetlands , Biological Oxygen Demand Analysis , Carbon Dioxide/chemistry , Methane/chemistry , Nitrogen/chemistry , Nitrous Oxide/chemistry , Phosphorus/chemistry , Water Pollutants/chemistry , Water Quality
17.
Environ Sci Pollut Res Int ; 28(37): 52124-52132, 2021 Oct.
Article in English | MEDLINE | ID: mdl-34002310

ABSTRACT

Phosphorus (P) removal efficiency of constructed wetland (CW) was limited due to the adsorption saturation on substrate surface along with continuous operation of CW. This study attempted to improve the P removal of CW through introduction of plant growth-promoting rhizobacteria (PGPR). Compared with the control-CW (C-CW), the results of CW with bio-augmentation (B-CW) showed that the total phosphorus (TP) removal efficiency was increased by 36.7% due to the enhanced plant uptake of P. The physiology indicators (height and root activity) of plants in B-CW were significantly improved, and the average P content of plants in B-CW was 0.78 g/kg, which was 85.7% higher than that of C-CW (0.42 g/kg). This was because PGPR addition optimized the P forms adsorbed on substrate surface and increased the proportion of Ca/Mg-P which was bioavailable for plant growth, and then subsequently enhanced plant uptake of P. Through bio-augmentation, the proportion of P removal by plant uptake in B-CW (25.2%) was increased by 2.5 times compared with that of C-CW (7.1%). The outcomes of this study would shed light on intensifying the role of plant uptake in P removal of CWs through bio-augmentation.


Subject(s)
Phosphorus , Wetlands , Adsorption , Nitrogen , Plants , Waste Disposal, Fluid
18.
J Ethnopharmacol ; 274: 114021, 2021 Jun 28.
Article in English | MEDLINE | ID: mdl-33716079

ABSTRACT

ETHNOPHARMACOLOGICAL RELEVANCE: Atopic dermatitis (AD) is a skin inflammatory disease characterized by erythema, eruption, lichenification and pruritus. Shi Zhen Formula (SZF), an empirical Chinese herbal preparation, has clinical efficacy in relieving the symptoms of AD patients. However, the underlying molecular mechanisms of SZF remained unclear. AIM OF THE STUDY: We aimed to investigate the anti-AD effects of SZF and elucidate its underlying molecular mechanisms using in vitro and in vivo models of AD. MATERIALS AND METHODS: High-performance liquid chromatography analysis was performed for quality control of SZF extract. The anti-inflammatory effect of SZF was investigated through evaluating the levels of nitric oxide (NO), chemokines and pro-inflammatory cytokines in the lipopolysaccharide (LPS) stimulated RAW264.7 cells. AD-like skin lesions in female BALB/c mice were induced by 2,4-dinitrochlorobenzene (DNCB). SZF (3.15, 6.30 and 9.45 g/kg) and dexamethasone (5 mg/kg) were administered by gavage daily for 15 consecutive days. The body weight, skin thickness, skin dermatitis severity and scratching behaviors were recorded throughout the study. Histological analysis, reverse transcription-quantitative polymerase chain reaction (RT-PCR), western blot (WB) and ELISA analysis were used to illuminate the molecular targets associated with the anti-AD effects of SZF. RESULTS: SZF markedly decreased the epidermal thickening and infiltration of mast cells in the ears and dorsal skin of the 2,4-dinitrochlorobenzene (DNCB)-treated mice. SZF not only suppressed the levels of immunoglobulin E (IgE), histamine, thymic stromal lymphopoietin (TSLP) and IL-4 in the serum but also suppressed the over-production of IL-4 and IL-6 and gene expressions of IL-4, IL-13, IL-31 and TSLP in the dorsal skin. Moreover, SZF improved epidermal barrier by increasing the protein expressions of filaggrin, involucrin and loricrin and inhibited the activation of NF-κB p65 pathway in the dorsal skin of the DNCB-treated mice. CONCLUSION: SZF alleviates DNCB induced AD-like skin lesions in mice through regulating Th1/Th2 balance, improving epidermal barrier and inhibiting skin inflammation. Our research findings provide scientific footing on the use of this Chinese herbal formula for the treatment of AD.


Subject(s)
Anti-Inflammatory Agents/pharmacology , Anti-Inflammatory Agents/therapeutic use , Dermatitis, Atopic/drug therapy , Drugs, Chinese Herbal/pharmacology , Drugs, Chinese Herbal/therapeutic use , Animals , Anti-Inflammatory Agents/chemistry , Cell Survival/drug effects , Cytokines/blood , Cytokines/metabolism , Dermatitis, Atopic/chemically induced , Dermatitis, Atopic/metabolism , Dermatitis, Atopic/pathology , Dinitrochlorobenzene/toxicity , Drugs, Chinese Herbal/chemistry , Female , Histamine/blood , Immunoglobulin E/blood , Interleukin-4/blood , Lipopolysaccharides/toxicity , Mast Cells/drug effects , Mice , Mice, Inbred BALB C , Models, Theoretical , NF-kappa B/metabolism , RAW 264.7 Cells , Skin/drug effects , Skin/pathology , Th1 Cells/metabolism , Th2 Cells/metabolism , Thymic Stromal Lymphopoietin
19.
Neurochem Res ; 46(4): 866-877, 2021 Apr.
Article in English | MEDLINE | ID: mdl-33453006

ABSTRACT

Hyperbaric oxygen (HBO) therapy is considered a safe and feasible method that to provide neuroprotection against ischemic stroke. However, the therapy mechanisms of HBO have not been fully elucidated. We hypothesized that the mechanism underlying the protective effect of HBO preconditioning (HBO-PC) against cerebral ischemia/reperfusion injury was related to inhibition of mitochondrial apoptosis and energy metabolism disorder. To test this hypothesis, an ischemic stroke model was established by middle cerebral artery occlusion (MCAO) in rats. HBO-PC involved five consecutive days of pretreatment before MCAO. In additional experiments, X chromosome-linked inhibitor of apoptosis protein (XIAP) and second mitochondria-derived activator of caspases (SMAC) shRNA and NC plasmids were intraventricularly injected into rat brains after MCAO (2 h). After 24 h, all rats underwent motor function evaluation, which was assessed by modified Garcia scores. TTC staining for the cerebral infarct and cerebral edema, and TUNEL staining for cell apoptosis, were also analyzed. Reactive oxygen species and antioxidative enzymes in rat brains were detected, as well as mitochondrial complex enzyme activities, ATP levels, and Na+/K+ ATPase activity. Western blot was used to detect apoptotic proteins including Bcl-2, Bax, caspase-3, caspase-9, cyc-c, XIAP, and SMAC. HBO-PC remarkably reduced the infarct volume and improved neurological deficits. Furthermore, HBO-PC alleviated oxidative stress and regulated the expression of apoptosis-related proteins. Moreover, HBO-PC inhibited the decrease in ATP levels, mitochondrial complex enzyme activities, and Na+/K+ ATPase activity to maintain stable energy metabolism. XIAP knockdown weakened the protective effect of HBO, whereas SMAC knockdown strengthened its protective effect. The effects of HBO-PC can be attributed to inhibition of ischemia/hypoxia-induced mitochondrial apoptosis and energy metabolism disturbance. The action of HBO-PC is related to the XIAP and SMAC signaling pathways.


Subject(s)
Apoptosis/physiology , Energy Metabolism/physiology , Hyperbaric Oxygenation , Infarction, Middle Cerebral Artery/therapy , Mitochondria/metabolism , Reperfusion Injury/therapy , Animals , Apoptosis Regulatory Proteins/genetics , Apoptosis Regulatory Proteins/metabolism , Gene Knockdown Techniques , Inhibitor of Apoptosis Proteins/genetics , Inhibitor of Apoptosis Proteins/metabolism , Ischemic Stroke/therapy , Male , Mitochondrial Proteins/genetics , Mitochondrial Proteins/metabolism , Rats, Sprague-Dawley
20.
Phytother Res ; 35(5): 2758-2772, 2021 May.
Article in English | MEDLINE | ID: mdl-33440458

ABSTRACT

Our previous study revealed that Epimedii Folium (EF) and Codonopsis Radix (CNR) significantly promoted tumor growth on a subcutaneous mouse model of prostate cancer (PCa) via enhancing the mRNA and protein expressions of androgen receptor (AR), while Astragali Radix (AGR) inhibited tumor growth via suppressing the protein expression of AR. In the present study, we aimed to investigate the potential interactions between EF, CNR or AGR and AR antagonist (abiraterone acetate [ABI]) on the tumor growth using subcutaneous and orthotopic PCa mouse models. EF, CNR, AGR and ABI were intragastrically given to mice once every 2 days for 4 weeks. The pharmacokinetics of ABI were evaluated in the plasma of rats when combined with EF, CNR, or AGR. Our results demonstrated that EF or CNR could weaken the anti-tumor effects of ABI via increasing the AR expression involving activation of the PI3K/AKT and Rb/E2F pathways and decreasing the bioavailability of ABI, while AGR could enhance the anti-tumor effects of ABI through suppressing the AR expression via inhibiting the activations of PI3K/AKT and Rb/E2F pathways and increasing the bioavailability of ABI. These findings imply that cautions should be exercised when prescribing EF and CNR for PCa patients.

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