ABSTRACT
Doxorubicin (DOX) is a widely utilized chemotherapeutic agent in clinical oncology for treating various cancers. However, its clinical use is constrained by its significant side effects. Among these, the development of cardiomyopathy, characterized by cardiac remodeling and eventual heart failure, stands as a major concern following DOX chemotherapy. In our current investigation, we have showcased the efficacy of MLN4924 in mitigating doxorubicin-induced cardiotoxicity through direct inhibition of the NEDD8-activating enzyme, NAE. MLN4924 demonstrated the ability to stabilize mitochondrial function post-doxorubicin treatment, diminish cardiomyocyte apoptosis, alleviate oxidative stress-induced damage in the myocardium, enhance cardiac contractile function, mitigate cardiac fibrosis, and impede cardiac remodeling associated with heart failure. At the mechanistic level, MLN4924 intervened in the neddylation process by inhibiting the NEDD8 activating enzyme, NAE, within the murine cardiac tissue subsequent to doxorubicin treatment. This intervention resulted in the suppression of NEDD8 protein expression, reduction in neddylation activity, and consequential manifestation of cardioprotective effects. Collectively, our findings posit MLN4924 as a potential therapeutic avenue for mitigating doxorubicin-induced cardiotoxicity by attenuating heightened neddylation activity through NAE inhibition, thereby offering a viable and promising treatment modality for afflicted patients.
Subject(s)
Cardiotoxicity , Cyclopentanes , Doxorubicin , Myocytes, Cardiac , NEDD8 Protein , Pyrimidines , Animals , Mice , Apoptosis/drug effects , Cardiotoxicity/drug therapy , Cardiotoxicity/pathology , Cardiotoxicity/prevention & control , Cardiotoxicity/etiology , Cardiotoxicity/metabolism , Cyclopentanes/pharmacology , Cyclopentanes/therapeutic use , Doxorubicin/adverse effects , Mice, Inbred C57BL , Myocytes, Cardiac/drug effects , Myocytes, Cardiac/metabolism , Myocytes, Cardiac/pathology , NEDD8 Protein/metabolism , NEDD8 Protein/antagonists & inhibitors , Oxidative Stress/drug effects , Pyrimidines/pharmacology , Ubiquitin-Activating Enzymes/antagonists & inhibitors , Ubiquitin-Activating Enzymes/metabolism , Ubiquitin-Activating Enzymes/geneticsABSTRACT
Three undescribed monoterpenoid indole alkaloid dimers (kopoffines A-C, which are connected via a methylene unit) and with nine known alkaloids were isolated and identified from the fruits of Kopsia arborea Blume. Their structures, including their absolute configurations, were established by HRESIMS, NMR, single-crystal X-ray diffraction, and ECD analyses. Kopoffines A-C showed significant inhibition against cyclin-dependent kinase 5 (IC50: 0.34-2.18 µM). Western blotting analyses showed that kopoffines A-C significantly decreased the protein levels of CDK5 and phospho-CDK5 (Tyr15) (pCDK5) at concentrations of 2.5 and 10 µM. The levels of phospho-Tau (Thr217) (pTau217, a new biomarker of AD), and phospho-Tau (Ser396) (pTau396), which play major roles in the formation of neurofibrillary tangles , were decreased by the kopoffines A-C treatment. Molecular docking studies indicated that kopoffines A-C could form stable interactions with CDK5.
Subject(s)
Apocynaceae , Secologanin Tryptamine Alkaloids , Apocynaceae/chemistry , Cyclin-Dependent Kinase 5 , Indole Alkaloids/chemistry , Molecular Docking Simulation , Molecular Structure , Monoterpenes , Phosphorylation , Secologanin Tryptamine Alkaloids/pharmacologyABSTRACT
Nineteen indole alkaloids including eleven new ones, taberdines A-K (1-11), were isolated from Tabernaemontana divaricata. Their structures were assigned by MS, NMR, single crystal X-ray diffractions, and ECD analyses. Alkaloid 1 is an aspidosperma-type monoterpenoid indole alkaloid and possesses a rearranged pyrrolidine moiety due to C-3 degradation, and 4 has a rare 1,3-oxazolidine moiety within iboga-type alkaloids. Alkaloids 2, 4, 6, and 11-19 combined with 5 µg/mL fluconazole exhibited significant activity to reverse fluconazole resistance in Candida albicans strains while no one used alone showed any activities against the resistant strain.
Subject(s)
Antifungal Agents/pharmacology , Candida albicans/drug effects , Drug Resistance, Fungal/drug effects , Fluconazole/pharmacology , Indole Alkaloids/pharmacology , Tabernaemontana/chemistry , Microbial Sensitivity Tests , Plant Leaves/chemistryABSTRACT
Two new monoterpenoid indole alkaloids, bousangines A (1) and B (2), were isolated from the twigs and leaves of Bousigonia angustifolia. Their structures including absolute configurations were elucidated by a combination of MS, NMR, ECD calculation, and single-crystal X-ray diffraction analysis. Bousangine A (1) possessed a rearrangement pentacyclic skeleton derived from aspidosperma-type alkaloids with C-17 degradation. Their antiproliferative activity against several human cancer cell lines were evaluated.
Subject(s)
Alkaloids/chemistry , Antineoplastic Agents, Phytogenic/pharmacology , Apocynaceae/chemistry , Antineoplastic Agents, Phytogenic/chemistry , Cell Line, Tumor , Humans , Models, Molecular , Molecular Structure , Paclitaxel/pharmacology , Vincristine/pharmacologyABSTRACT
Pure CuC2O4·xH2O and CuC2O4·xH2O/carbon nanotubes (CNTs) composites are synthesized by a low-temperature hydrothermal process. The structure and morphology of the products are analyzed by X-ray diffraction (XRD), scanning electron microscopy (SEM), thermogravimetric analysis (TG) and Raman spectrum. The results demonstrate that the as-prepared CuC2O4·xH2O takes on a microsphere-like morphology, all CuC2O4·xH2O/CNTs nanocomposites are constructed by the intertwining of tabular CuC2O4·xH2O nanoparticles (NPs) and CNTs to form a tanglesome net. When evaluated as an anode materials for lithium ion batteries (LIBs), all CuC2O4·xH2O/CNTs electrodes possess higher reversible discharge capacities (more than 1000 mAh g-1) than the pure CuC2O4·xH2O, up to 200th cycle at a current density of 100 mA g-1. The results illustrate that the addition of CNTs can enhance the electrochemical performance of CuC2O4·xH2O. Overall, CuC2O4·xH2O/CNTs composite can be a promising candidate used as a promising anode for LIBs.
ABSTRACT
OBJECTIVE: To conclude of the technical notes of percutaneous transforaminal endoscope-assisted lumbar interbody fusion (PT-Endo-LIF), and to investigate its safety and efficacy for treatment of degenerative lumbar disease. METHODS: Twenty-four patients were treated by PT-Endo-LIF combined with posterior percutaneous pedicle screws fixation from October 2017 to April 2018. There were 16 males and 8 females, ranging in age from 39 to 72 years old, with a mean of (59.6±9.5) years old. There were 15 cases diagnosed with lumbar intervertebral disc herniation combined with degenerative disc, the other 9 cases were diagnosed as low level lumbar spondylolistheses w/o segmental instability. Single segmental fusion was performed for 22 cases(one for L2,3, 3 for L3,4 and 18 for L4,5) and 2 segmental fusion was performed for the other 2 cases (both for L3,4 and L4,5). PT-Endo-LIF was performed under local anesthesia with conscious sedation, followed by decompression through endoscopic technics. After that, end-plate preparation and autogenous bone and expandable cage implantation were performed. Finally, percutaneous screws and rod instrumentation were used. The visual analogue scale (VAS) and Oswestry Disability Index (ODI) were used to evaluate the clinical efficacy. The operation time, intraoperative bleeding volume, intraoperative and postoperative complications were recorded. All patients underwent X-ray, CT plain scan, three-dimensional reconstruction and MRI examination to evaluate the stability of the implants and fusion rate before 3 days and 1, 3, 6, 12 and 18 months after operation. RESULTS: All patients were followed up, and the duration ranged from 12 to 18 months. The operation time of single-segment fusion was (192.3±22.7) min, and that of double-segment fusion was (272.5±24.7) min. The estimated intraoperative bleeding volume was less than 50 ml per segment, and no blood transfusion was performed in all patients. The VAS improved from preoperative 7.4±1.1 to postoperative 2.3±0.8 (t=-19.65, P<0.000 5). The ODI improved from preoperative (41.2±3.3)% to the final follow-up (12.3±2.5)%(t=-35.76, P<0.000 5). Postoperative complications occurred in 4 cases, and contralateral radicular symptoms occurred in 2 cases. After contralateral foraminoscopic decompression, the symptoms were completely alleviated. One case had neurological symptoms related to percutaneous screw placement, and the symptoms were alleviated after removal of the lateral screw rod internal fixation. The other cases had surgical incision infection and improved after debridement and suture. At the latest follow-up, no displacement or loosening of the fusion cage and screw rod system occurred in all patients, and 14 cases showed signs of fusion. CONCLUSIONS: PT-Endo-LIF is a minimal invasive, safe and efficient surgical procedure for treatment of degenerative lumbar disease. Nevertheless, the long-term results still need to be confirmed by a multi-center and lagre sample follow-up study.
Subject(s)
Intervertebral Disc Degeneration , Spinal Fusion , Adult , Aged , Female , Follow-Up Studies , Humans , Lumbar Vertebrae , Male , Middle Aged , Neuroendoscopy , Treatment OutcomeABSTRACT
Five new monoterpenoid indole alkaloids, melotenuines A-E (1-5), along with 18 known indole alkaloids, were isolated from the twigs and leaves of Melodinus tenuicaudatus. The structures of the new alkaloids were determined by a combination of MS, NMR and ECD analysis. Melotenuine A (1) represents the first example of aspidosperma-meloscandonine type bisindole alkaloids characterized by a methylene bridge between the two monomers, while melotenuine B (2) possessed a rare eburnamine-melsocandonine skeleton. All of the new indole alkaloids were evaluated for in vitro cytotoxicities against five human cancer cell lines. Among them, alkaloid 4 showed specific cytotoxicity against HL-60 cell line with IC50 value (5.15⯱â¯0.16⯵M) comparable with that of positive control.
Subject(s)
Antineoplastic Agents, Phytogenic/pharmacology , Apocynaceae/chemistry , Plant Leaves/chemistry , Secologanin Tryptamine Alkaloids/pharmacology , Antineoplastic Agents, Phytogenic/isolation & purification , Cell Line, Tumor , China , Drug Screening Assays, Antitumor , HL-60 Cells , Humans , Molecular Structure , Phytochemicals/isolation & purification , Phytochemicals/pharmacology , Secologanin Tryptamine Alkaloids/isolation & purificationABSTRACT
microRNA (miR/miRNA)-27a-3p has been reported to be abnormally expressed in various types of cancer, including colorectal cancer (CRC). B-cell translocation gene 1 (BTG1) has also been implicated with CRC. However, the association between miR-27a-3p and BTG1 in CRC, to the best of our knowledge, has not been investigated. In order to assess whether miR-27a-3p is associated with CRC, reverse transcription-quantitative PCR was performed on 20 paired CRC and paracancerous tissues for miRNA analysis. For the screening and validation of miR-27a-3p expression in colon cancer, several colon cancer cell lines (HCT-116, HCT8, SW480, HT29, LOVO and Caco2) and the normal colorectal epithelial cell line NCM460 were examined. The highest expression levels of miR-27a-3p were detected in the HCT-116, which was selected for further experimentation. The HCT-116 cells were divided into control, miR-27a-3p mimic and inhibitor groups, and cell proliferation was tested using an MTT assay. Additionally, miR-27a-3p inhibitor/mimic or BTG1 plasmid were transfected into the HCT-116 cells, and flow cytometry was performed to analyze cell cycle distributions. TUNEL analysis was performed to detect apoptosis. Protein levels of factors in the downstream signaling pathway mediated by miR-27a-3p [ERK/mitogen-activated extracellular signal-regulated kinase (MEK)] were detected. miR-27a-3p was revealed to be overexpressed in human CRC tissues and colon cancer cell lines. Knockdown of miR-27a-3p suppressed proliferation of HCT-116 cells and apoptosis was increased. It further markedly upregulated expression levels of BTG1 and inhibited activation of proteins of the ERK/MEK signaling pathway. In addition, overexpression of BTG1 in HCT-116 cells triggered G1/S phase cell cycle arrest and increased apoptosis via the ERK/MEK signaling pathway. In conclusion, the present study demonstrated that the effects of miR-27a-3p on colon cancer cell proliferation and apoptosis were similar to those of the tumor suppressor gene BTG1. The miR-27a-3p/BTG1 axis may have potential implications for diagnostic and therapeutic approaches in CRC.
ABSTRACT
Developmental lead (Pb) exposure involves various serious consequences, especially leading to neurotoxicity. In this study, we examined the possible role of monosialoganglioside (GM1) in lead-induced nervous impairment in the developing rat. Newborn male Sprague-Dawley rat pups were exposed to lead from birth for 30 days and then subjected to GM1 administration (0.4, 2, or 10 mg/kg; i.p.) or 0.9% saline. The results showed that developmental lead exposure significantly impaired spatial learning and memory in the Morris water maze test, reduced GM1 content, induced oxidative stress, and weakened the antioxidative systems in the hippocampus. However, co-treatment with GM1 reversed these effects. Moreover, GM1 counteracted lead-induced apoptosis by decreasing the expression of Bax, cleaved caspase-3, and by increasing the level of Bcl-2 in a dose-dependent manner. Furthermore, we found that GM1 upregulated the expression of SIRT1, CREB phosphorylation, and BDNF, which underlie learning and memory in the lead-treated developing rat hippocampus. In conclusion, our study demonstrated that GM1 exerts a protective effect on lead-induced cognitive deficits via antioxidant activity, preventing apoptosis, and activating SIRT1/CREB/BDNF in the developing rat hippocampus, implying a novel potential assistant therapy for lead poisoning.
Subject(s)
Brain Injuries/drug therapy , Cognitive Dysfunction/drug therapy , G(M1) Ganglioside/pharmacology , Hippocampus/drug effects , Neuroprotective Agents/pharmacology , Animals , Apoptosis/drug effects , Brain Injuries/chemically induced , Brain-Derived Neurotrophic Factor/metabolism , Cognitive Dysfunction/chemically induced , Cyclic AMP Response Element-Binding Protein/metabolism , Female , Hippocampus/metabolism , Hippocampus/pathology , Lead , Male , Rats , Rats, Sprague-Dawley , Sirtuin 1/metabolismABSTRACT
Thermogravimetric-Fourier Transform Infrared Spectroscopy was conducted to evaluate the combustion characteristics of refuse derived fuel (RDF) adding of microwave chlorine depleted pyrolyzate in the mass proportion of 5-15%. It studied the catalyze effect of chlorine depleted pyrolyzate on RDF combustion performance. The combustion process of RDF could be divided into four stages. The temperature range of the most significant combustion stage of 10-RDF was much more extensive than another three ones. According to the FTIR analysis, the addition of chlorine depleted pyrolyzate might promote the combustion of CH4 and carbonyls to CO2 and H2O earlier. Based on the distributed activation energy model (DAEM), the E value of RDF with chlorine depleted pyrolyzate added was much lower than that with no chlorine depleted pyrolyzate added. The chlorine depleted pyrolyzate enhanced the combustion performance of RDF with the lower ignition, lower burnout temperature, better combustion ability, better flammability and more outstanding combustion performance. The best combustion characteristic was obtained when the dosage of chlorine depleted pyrolyzate was 10%.
Subject(s)
Garbage , Refuse Disposal , Chlorine , Microwaves , TemperatureABSTRACT
OBJECTIVE: Escape from the body's immune response is a basic characteristic of lung cancer, and indoleamine-2,3-dioxygenase (IDO) plays a key role in mediating immune escape of non-small-cell lung cancer, which leads to recurrence and metastasis. Feiji Recipe, a compound Chinese herbal medicine, has the effect of stabilizing lesions and prolonging survival in patients with lung cancer. The purpose of this study was to investigate the mechanisms underlying the anticancer properties of Feiji Recipe. METHODS: An orthotopic transplant model of mouse Lewis lung cancer, with stable expression of IDO gene, was established in C57BL/6 mice. Optical imaging was used to observe the effects of Feiji Recipe in the treatment of lung cancer in vivo. The effects of Feiji Recipe on the proliferation of mouse Lewis lung cancer cell line 2LL, 2LL-enhanced green fluorescent protein (2LL-EGFP) and 2LL-EGFP-IDO were investigated, and the apoptosis of T-cells was examined by 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2H-tetrazolium bromide using flow cytometry. Chemical composition of Feiji Recipe was validated by high-performance liquid chromatography. RESULTS: Compared to the control group, the survival of animals treated with Feiji Recipe was significantly prolonged (Pâ¯=â¯0.0074), and the IDO protein level decreased (Pâ¯=â¯0.0072); moreover, the percentages of CD4+CD25+ T-cells and Foxp3+ T-cells were significantly decreased (Pâ¯<â¯0.05). The molecular mechanism of Feiji Recipe against lung cancer may relate to the regulation of immune cells, such as T-cells and regulatory T-cells. CONCLUSION: The molecular mechanism of Feiji Recipe in treatment of lung cancer is to restore the function of T-cells in the cancer microenvironment through interfering with the IDO pathway.
Subject(s)
Carcinoma, Lewis Lung/drug therapy , Cell Proliferation/drug effects , Drugs, Chinese Herbal/administration & dosage , Growth Inhibitors/administration & dosage , Indoleamine-Pyrrole 2,3,-Dioxygenase/immunology , Lung Neoplasms/drug therapy , Animals , Apoptosis/drug effects , Carcinoma, Lewis Lung/enzymology , Carcinoma, Lewis Lung/immunology , Carcinoma, Lewis Lung/physiopathology , Disease Models, Animal , Humans , Indoleamine-Pyrrole 2,3,-Dioxygenase/genetics , Lung Neoplasms/enzymology , Lung Neoplasms/immunology , Lung Neoplasms/physiopathology , Male , Mice , Mice, Inbred C57BL , T-Lymphocytes, Regulatory/drug effects , T-Lymphocytes, Regulatory/immunologyABSTRACT
This study aims to investigate the menstrual recovery outcome of scar pregnancy patients who received uterine artery embolization combined with curettage, and its influencing factors.The data of 119 patients with scar pregnancy, who received uterine artery embolization combined with curettage between December 2012 and December 2016 in Henan Provincival People's Hospital, were collected. The menstruation recovery of these patients was followed up, and factors that have influence on menstrual blood volume were analyzed using SPSS V.17.0.Follow-up data were available in 101/119 (84.9%) women. The median follow-up time was 22.7 months (range: 1.6-50.6 months); 58 (57.4%) patients had reduced menstrual blood volume, and 2 patients (2%) had amenorrhea. The proportion of patients with reduced menstrual blood volume, who were embolized with polyvinyl alcohol (PVA), PVA combined with gelatin sponge, and gelatin sponge between < and ≥33 years old was 41.7% versus 66.7%, 40% versus 57.1% and 60.6% versus 68.0%. The average age of patients with reduced menstrual blood volume (34.3 years) was greater than patients with normal menstrual blood volume (31.4 years), but the difference was not statistically significant (Pâ=â.07).Reduced menstrual blood volume can occur in scar pregnancy patients who received uterine artery embolization combined with curettage. The influence of the embolic agent PVA on menstrual blood volume depends on age, but the difference was not statistically significant.
Subject(s)
Blood Loss, Surgical/prevention & control , Curettage/adverse effects , Menstruation Disturbances , Postoperative Complications , Pregnancy, Ectopic , Uterine Artery Embolization/methods , Uterine Rupture/prevention & control , Abortion, Legal/adverse effects , Abortion, Legal/methods , Adult , Cesarean Section/adverse effects , Cicatrix/etiology , Cicatrix/pathology , Cicatrix/physiopathology , Curettage/methods , Female , Humans , Long Term Adverse Effects/diagnosis , Menstruation Disturbances/diagnosis , Menstruation Disturbances/etiology , Postoperative Complications/diagnosis , Postoperative Complications/physiopathology , Pregnancy , Pregnancy, Ectopic/diagnosis , Pregnancy, Ectopic/surgery , Recovery of Function , Uterine Rupture/etiologyABSTRACT
Recoveries of cobalt and lithium metals from spent lithium-ion batteries are very important for prevention of environmental pollution and alleviation of resource shortage. In this study, a hydrometallurgical route for the recovery of lithium fluoride was proposed. Lithium and cobalt could be first selectively leached into solution using formic acid and hydrogen peroxide. By investigating the effects of leaching temperature, time, stoichiometric ratio, H2O2 concentration and solid-to-liquid ratio, the leaching efficiency of Li and Co could reach 99.90% and 99.96%, respectively. Meanwhile, the evaluation of leaching kinetics and calculation of apparent activation energies revealed that the leaching process fitted chemical control satisfactorily. After further fractional precipitation, a high purity of 99.0% lithium fluoride could be finally obtained, thus achieving the effective recovery of spent material from the lithium-ion battery.
ABSTRACT
PPARα and PPARγ have been the most widely studied Peroxisome proliferator-activated receptor (PPAR) subtypes due to their important roles in regulating glucose, lipids, and cholesterol metabolism. By combining the lowering serum triglyceride levels benefit of PPARα agonists (such as fibrates) with the glycemic advantages of the PPARγ agonists (such as TZD), the dual PPAR agonists approach can both improve the metabolic effects and minimize the side effects caused by either agent alone, and hence, has become a promising strategy for designing effective drugs against type-2 diabetes. In this study, by means of virtual screening, ADMET prediction and molecular dynamics (MD) simulations techniques, one compound-ASN15761007 with high binding score, low toxicity were gained. It was observed by MD simulations that ASN15761007 not only possessed the same function as AZ242 did in activating PPARα and BRL did in activating PPARγ, but also had more favorable conformation for binding to the two receptors. Our results provided an approach to rapidly produce novel PPARα/γ dual agonists which might be a potential lead compound to develop against insulin resistance and hyperlipidemia.
Subject(s)
Drug Design , Molecular Docking Simulation , Molecular Dynamics Simulation , PPAR alpha/chemistry , PPAR gamma/chemistry , Amino Acid Sequence , Amino Acids/chemistry , Binding Sites , Computer Simulation , Ligands , Molecular Conformation , PPAR alpha/agonists , PPAR gamma/agonists , Protein Binding , Quantitative Structure-Activity RelationshipABSTRACT
The thiazolidinedione class PPARγ agonists as antidiabetic agents are restricted in clinical use because of the side effects such as edema, weight gain, and heart failure. The single and selective agonism of PPARγ is the main cause of side effects. The multi-target cooperative PPARα/γ dual agonist development is a hot topic in the antidiabetic medicinal chemistry field. Saroglitazar is the first approved PPARα/γ dual agonist, available in India for the treatment of diabetic dyslipidemia. It got rid of these side effects. With the aim of finding more protent PPARα/γ dual agonists, the scaffold hopping was used to replace α-o phenylpropionic acid skeleton of saroglitazar with L-tyrosine skeleton. Then, the structural modification was carried out designing 72 compounds. Considering the importance of chirality, opposite configuration of 72 compounds was also studied. 12 compounds with better -cdocker energy were screened by molecular docking. Subsequently, the pharmacokinetic properties and toxicity evaluated by ADMET prediction, 11 of them showed better properties. Comp#L-17-1 and comp#L-3-1 were regarded as representatives to study the binding stability by molecular dynamics (MD) simulations. The MD simulation results of comp#L-17-1-PPARs (α, γ) and comp#L-3-1-PPARs (α, γ) provided structure reference for the research and development of novel PPARα/γ dual agonists.
Subject(s)
Drug Discovery/methods , Hypoglycemic Agents/chemistry , PPAR alpha/agonists , PPAR gamma/agonists , Phenylpropionates/chemistry , Pyrroles/chemistry , Diabetes Mellitus/drug therapy , Dyslipidemias/drug therapy , Humans , Hypoglycemic Agents/pharmacology , Molecular Docking Simulation , Molecular Dynamics Simulation , Phenylpropionates/pharmacology , Pyrroles/pharmacologyABSTRACT
The present study focuses on pretreatment of enhancing the properties of refuse-derived fuel (RDF) via low-temperature microwave irradiation. These improved properties include lower chlorine content, a more porous surface structure and better combustion characteristics. In this study, low-temperature microwave irradiation was carried out in a modified microwave apparatus and the range of temperature was set to be 220-300â. We found that the microwave absorbability of RDF was enhanced after being partly carbonized. Moreover, with the increasing of the final temperature, the organochlorine removal ratio was greatly increased to 80% and the content of chlorine was dramatically decreased to an extremely low level. It was also interesting to find that the chlorine of RDF was mainly released as HCl rather than organic chloride volatiles. The finding is just the same as the polyvinyl chloride pyrolysis process. In addition, pores and channels emerged during the modifying operation and the modified RDF has better combustibility and combustion stability than traditional RDF. This work revealed that low-temperature modification of RDF via microwave irradiation is significant for enhancing the quality of RDF and avoiding HCl erosion of equipment substantially.
Subject(s)
Garbage , Microwaves , Chlorine , Conservation of Energy Resources , Polyvinyl Chloride , TemperatureABSTRACT
In order to form a modified solid recovered fuel (SRF) with low chlorine content, high calorific value and well combustion performance, low temperature microwave irradiation was applied to remove the chlorine of the organochloride waste mixture before they were mixed to form SRF. The optimizing conditions of final temperature, microwave absorbents and heating rate were also detected to obtain high dechlorination ratio and high ratio of hydrogen chloride (HCl) to volatiles. In the temperature range of 220-300°C, 280°C would be chose as the optimal low microwave modified temperature concerning at which the dechlorination ratio was high and ratio of HCl to volatiles was relatively high as well; The use of microwave absorbents of graphite and silicon carbide (SiC) had a pronounced effect on the dechlorination of organochloride waste mixture, and the dechlorination ratio was increased significantly which could be reached to 87%, almost 20% higher than absorbent absent sample; The heating rate should set be not too fast nor too slow, and there was no big difference between the heating rate of 13°C/min and 15°C/min; The content of Cl of modified SRF is dramatically decreased and reaches to a low level 0.328%. Hence, the modified SRF can be ascended from the third class to the second class according to the Finland chlorine Classes I-III. Moreover, the combustibility of modified SRF was substantial improved compared to the traditional SRF. The low heating value was almost 20.56MJ/kg which is close to the LHV of lignite coal and bituminous coal in China, and it increased by 60% over that of traditional SRF. Removing chlorine of organochloride waste mixture before they are mixed with other kinds of combustible waste to form a modified SRF which is expected to be an alternative fuel for combustion in the future.
Subject(s)
Hydrocarbons, Chlorinated/radiation effects , Microwaves , Refuse Disposal/methods , Solid Waste , Energy-Generating Resources , Halogenation , Hydrocarbons, Chlorinated/chemistry , RecyclingABSTRACT
The present study was performed to investigate the role of p38 mitogenactivated protein kinase (MAPK) in the resorption of herniated intervertebral discs in 30 rats. In the noncontained and p38 MAPK inhibition (p38i) groups, two coccygeal intervertebral discs (IVDs) were removed and wounded prior to relocation into the subcutaneous space of the skin of the back. In the contained group, the cartilage endplates maintained their integrity. Furthermore, SB203580 was injected intraperitoneally into the p38i group, whereas saline was injected into the other two groups. In the noncontained group, the weight of the relocated IVDs decreased to a greater extent over time when compared with the contained and p38i groups. Phosphorylated p38, tumor necrosis factorα, and interleukin1ß were observed to exhibit higher expression levels in the noncontained group compared with the contained and p38i groups, at weeks 1 and 4 postsurgery. The expression level of caspase3 and the densities of apoptotic disc cells were significantly higher in the noncontained group compared with the contained and p38i groups at 4 weeks postsurgery. In conclusion, p38 MAPK induces apoptosis in IVDs, while also accelerating the resorption of the relocated IVDs. Thus, p38 MAPK may be important in spontaneous resorption of IVDs.
Subject(s)
Apoptosis/drug effects , Imidazoles/pharmacology , Intervertebral Disc Displacement/drug therapy , Intervertebral Disc/enzymology , Pyridines/pharmacology , p38 Mitogen-Activated Protein Kinases/antagonists & inhibitors , Animals , Caspase 3/metabolism , Intervertebral Disc/pathology , Intervertebral Disc Displacement/enzymology , Intervertebral Disc Displacement/pathology , Male , Rats , Rats, Sprague-Dawley , p38 Mitogen-Activated Protein Kinases/metabolismABSTRACT
Targeted drug delivery systems, especially those that use nanoparticles, have been the focus of research into cancer therapy during the last decade, to improve the bioavailability and delivery of anticancer drugs to specific tumor sites, thereby reducing the toxicity and side effects to normal tissues. However, the positive antitumor effects of these nanocarriers observed in conventional monolayer cultures frequently fail in vivo, due to the lack of physical and biological barriers resembling those seen in the actual body. Therefore, the collagen-based 3-D multicellular culture system, to screen new nanocarriers for drug delivery and to obtain more adequate and better prediction of therapeutic outcomes in preclinical experiments, was developed. This 3-D culture model was successfully established using optimized density of cells. Our result showed that 3-D cell colonies were successfully developed from 95-D, U87 and HCT116 cell lines respectively, after a seven-day culture in the collagen matrix. The coumarin-conjugated nanoparticles were able to penetrate the matrix gel to reach the tumor cells. The model is supposedly more accurate in reflecting/predicting the dynamics and therapeutic outcomes of candidates for drug transport in vivo, and/or investigation of tumor biology, thus speeding up the pace of discovery of novel drug delivery systems for cancer therapy.
Subject(s)
Collagen/chemistry , Drug Carriers/chemistry , Nanoparticles/chemistry , Spheroids, Cellular/drug effects , Antineoplastic Agents/chemistry , Antineoplastic Agents/pharmacology , Biological Transport , Cell Count , Cell Line, Tumor , Drug Carriers/toxicity , Humans , Nanoparticles/metabolism , Nanoparticles/toxicity , Spheroids, Cellular/cytology , Spheroids, Cellular/metabolismABSTRACT
Traditional chemotherapeutic drugs remain the major treatment for advanced colorectal cancer. However, due to the lack of tumor specificity these drug also destroy healthy tissue and organs, which has been the main reason for treatment failure and mortality. Folate-based drug delivery systems for improving nanoparticle endocytosis have been used to address these problems. Here, folic acid (FA) conjugated mPEG-b-P(CABCL-co-ACL) diblock copolymers were synthesized and characterized by TEM and NMR. Drug loaded nanoparticles were prepared using dialysis method and was obtained with a mean diameter of 45.2 nm with sustained in vitro release profile. In vitro cytotoxicity assay indicated that the cytotoxicity of folate modified nanoparticles were significantly increased compared to free drug and non-folate nanoparticles. In addition, results of hemolytic and histopathologic study suggested that the non-loaded nanoparticle (NL/NP) was non-toxic and biocompatible at the testing concentration. Moreover, in vivo results showed that FA/5-FU/NP effectively inhibited growth of HCT-8 cell-based xenograft tumors in BALB/c mice and revealed stronger antitumor efficacy than other treated groups. Thus, both in vitro and in vivo results exhibited that the folate conjugated mPEG-b-P(CABCL-co-ACL) copolymers have great potential to be used as sustainable and specific colon cancer targeting delivery system for anticancer agents.