ABSTRACT
Targeted assembly of nanoparticles in biological systems holds great promise for disease-specific imaging and therapy. However, the current manipulation of nanoparticle dynamics is primarily limited to organic pericyclic reactions, which necessitate the introduction of synthetic functional groups as bioorthogonal handles on the nanoparticles, leading to complex and laborious design processes. Here, we report the synthesis of tyrosine (Tyr)-modified peptides-capped iodine (I) doped CuS nanoparticles (CuS-I@P1 NPs) as self-catalytic building blocks that undergo self-propelled assembly inside tumour cells via Tyr-Tyr condensation reactions catalyzed by the nanoparticles themselves. Upon cellular internalization, the CuS-I@P1 NPs undergo furin-guided condensation reactions, leading to the formation of CuS-I nanoparticle assemblies through dityrosine bond. The tumour-specific furin-instructed intracellular assembly of CuS-I NPs exhibits activatable dual-modal imaging capability and enhanced photothermal effect, enabling highly efficient imaging and therapy of tumours. The robust nanoparticle self-catalysis-regulated in situ assembly, facilitated by natural handles, offers the advantages of convenient fabrication, high reaction specificity, and biocompatibility, representing a generalizable strategy for target-specific activatable biomedical imaging and therapy.
Subject(s)
Nanoparticles , Neoplasms , Humans , Furin , Phototherapy , Neoplasms/diagnostic imaging , Neoplasms/therapy , Nanoparticles/chemistry , Catalysis , Copper/chemistryABSTRACT
Introduction: Antidepressants are the front-line treatments for major depressive disorder (MDD), but remain unsatisfactory in outcome. An increasing number of patients are interested in acupuncture and moxibustion treatment as complementary therapies. This study aims to evaluate the efficacy and safety of integrative acupuncture and moxibustion (iAM) treatment in patients with MDD. Methods and Analysis: This multicenter, single-blind, 2 × 2 factorial randomized trial will enroll 592 patients with MDD of moderate severity from nine hospitals. All patients will be randomized, in a ratio of 2:2:2:1, through a computerized central randomization system, into four groups (the combined, iAM-only, sertraline-only, and placebo groups). Participants will undergo a 12-week intervention with either 50 mg of sertraline or a placebo once a day and active/sham iAM treatment three times per week. The primary outcome is depression severity, assessed using the Hamilton Depression Scale-17. The secondary outcomes include self-rated depression severity, anxiety, and sleep quality. The primary and secondary outcomes will be measured at weeks 0, 4, 8, 12, and the 8th week posttreatment. Safety will be evaluated through liver and kidney function tests conducted before and after treatment and through monitoring of daily adverse events. An intent-to-treat principle will be followed for the outcome analyses. Conclusion: This trial will provide sufficient evidence to ascertain whether iAM is effective and safe for treating MDD and provides a suitable combination strategy for treating MDD. Clinical Trial Registration: [www.chictr.org.cn], identifier [ChiCTR2100042841].
ABSTRACT
RATIONALE: Bear bile powder (BBP) is a widely used traditional Chinese medicine (TCM), and bile acids (BAs) are the main active components in BBP. Due to the scarcity of BBP resources, adulterations often occur in the market. Conventional methods to distinguish them are usually complicated and time-consuming. To enhance effectiveness and accuracy, a rapid and rough analytical method is desperately needed. METHODS: In this study, a rapid strategy using chip-based nano-electrospray ionization tandem mass spectrometry (nano-ESI-MS/MS) was established to distinguish BBP from other sources of bile powder (BP). In addition, the results were further verified by ultra-high-performance liquid chromatography combined with high-resolution mass spectrometry (UPLC/MS). RESULTS: The precision of the chip-based nano-ESI-MS/MS method was validated to be acceptable with relative standard deviation (RSD) <15%. The distinction between BBP and other sources of BP, including common adulterants of pig bile powder (PBP), cattle bile powder (CBP), sheep bile powder (SBP), and chicken bile powder (CkBP), can be observed in the spectra. By using orthogonal partial least-squares discriminant analysis (OPLS-DA), more potential m/z markers were investigated. A BAs-related m/z marker of 498.3 was discovered as a typical differential molecular ion peak and was identified as tauroursodeoxycholic acid (TUDCA) and taurochenodeoxycholic acid (TCDCA) in BBP. CONCLUSIONS: The proposed strategy has simple sample pretreatment steps and significantly shortened analysis time. As an emerging technology, chip-based nano-ESI-MS not only provides a reference for the rapid distinction of adulterated Chinese medicines, but also provides some insights into the identification of other chemicals and foods.
Subject(s)
Bile , Ursidae , Animals , Bile/chemistry , Bile Acids and Salts/analysis , Cattle , Chromatography, High Pressure Liquid/methods , Powders/analysis , Sheep , Spectrometry, Mass, Electrospray Ionization/methods , Swine , Tandem Mass Spectrometry/methodsABSTRACT
Emodin nanostructured lipid carriers(ED-NLC) were prepared and their quality was evaluated in vitro. Based on the results of single-factor experiments, the ED-NLC formulation was optimized by Box-Behnken response surface method with the dosages of emodin, isopropyl myristate and poloxamer 188 as factors and the nanoparticle size, encapsulation efficiency and drug loading as evaluation indexes. Then the evaluation was performed on the morphology, size and in vitro release of the nanoparticles prepared by emulsification-ultrasonic dispersion method in line with the optimal formulation, i.e., 3.27 mg emodin, 148.68 mg isopropyl myristate and 173.48 mg poloxamer 188. Under a transmission electron microscope(TEM), ED-NLC were spherical and their particle size distribution was uniform. The particle size of ED-NLC was(97.02±1.55) nm, the polymer dispersion index 0.21±0.01, the zeta potential(-38.96±0.65) mV, the encapsulation efficiency 90.41%±0.56% and the drug loading 1.55%±0.01%. The results of differential scanning calorimeter(DSC) indicated that emodin may be encapsulated into the nanostructured lipid carriers in molecular or amorphous form. In vitro drug release had obvious characteristics of slow release, which accorded with the first-order drug release equation. The fitting model of Box-Behnken response surface methodology was proved accurate and reliable. The optimal formulation-based ED-NLC featured concentrated particle size distribution and high encapsulation efficiency, which laid a foundation for the follow-up study of ED-NLC in vivo.
Subject(s)
Emodin , Nanostructures , Drug Carriers , Follow-Up Studies , LipidsABSTRACT
BACKGROUND: Parkinson disease (PD) is a common neurodegenerative disease among middle-aged and elderly people. Clinically, it is a movement disorder characterized mainly by static tremors, kinesia, myotonia, and postural balance disorder. In recent years, an increasing number of clinical reports on moxibustion therapy for PD have been published. Despite this, no systematic review of moxibustion therapy for PD has been undertaken. METHODS: Two reviewers will search the following 7 English and Chinese databases online: the Cochrane Library; PubMed; EMBASE; the China National Knowledge Infrastructure; the Wan Fang databases; the China Science and Technology Journal Database; and the Chinese Biomedical Literature Database. Reviewers will search each electronic database for studies published from journal inception to May 2021. Two reviewers will independently conduct clinical study inclusion, data extraction, and risk bias assessment. Any differences in the above process will be resolved through discussion with a third reviewer. If the data are sufficient, RevMan software 5.3 (Cochrane Community, London, UK) will be used for the meta-analysis of the extracted data. RESULTS: In this systematic review, the effectiveness and safety of moxibustion therapy in PD treatment will be evaluated. CONCLUSION: This systematic review may provide further evidence to encourage clinicians to use moxibustion in the treatment of PD. INPLASY REGISTRATION NUMBER: INPLASY202140097.
Subject(s)
Moxibustion , Parkinson Disease/therapy , Humans , Meta-Analysis as Topic , Moxibustion/adverse effects , Moxibustion/methods , Research Design , Systematic Reviews as Topic , Treatment OutcomeABSTRACT
An amendment to this paper has been published and can be accessed via a link at the top of the paper.
ABSTRACT
Aim: Diosbulbin B (DB) is a major diterpenoid compound found in Dioscorea bulbifera L, a traditional medicinal herb in China. Clinical reports have confirmed that Dioscorea bulbifera L. can induce significant hepatotoxicity. In this study, we showed that DB can induce mitochondria-dependent apoptosis and investigated the role of autophagy in DB-induced hepatotoxicity in L-02 hepatocytes. Methods: L-02 hepatocytes were treated with different concentrations of DB for 48 h, after which indicators of autophagy and apoptosis were measured. 3-Methyladenine (3-MA) and rapamycin (Rapa) were used as inhibitor and agonist of autophagy, respectively. Furthermore, the reactive oxygen species (ROS) scavenger N-acetyl-l-cysteine (NAC) was used in combination with DB to evaluate the relationship between ROS and autophagy. Results: L-02 cell viability was significantly decreased after treatment with DB for 48 h. Additionally, DB induced concentration-dependent apoptosis and autophagy and increased the activities of caspase-3, caspase-9, alanine aminotransferase (ALT), and aspartate transaminase (AST), and induced excessive leakage of lactate dehydrogenase (LDH). Inhibition of autophagy by 3-MA increased DB-induced apoptosis, resulting in aggravation of hepatotoxicity. Conversely, treatment with Rapa increased malondialdehyde (MDA) content and reduced superoxide dismutase (SOD) activity. Moreover, we found that DB treatment increased the level of intracellular ROS, decreased the mitochondrial membrane potential (MMP) and adenosine triphosphate (ATP) production, and caused abnormal opening of the mitochondrial permeability transition pore (mPTP), which were finally restored by the ROS scavenger NAC. Conclusions: Accumulation of ROS can induce mitochondria-dependent apoptosis and likely to play a key role in DB-induced hepatocellular injury. Activation of autophagy may inhibit apoptosis, but also reduces antioxidant capacity.
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Hepatitis B is one of most etiologies of Liver cirrhosis in China, and clinically lacks the effective strategy for Hepatitis B caused cirrhosis (HBC) therapy. As a complementary and alternative medicine, Chinese Traditional Medicine (TCM) has special therapeutic effects for HBC. Here, we focus on the evolution process of HBC TCM syndromes, which was from Excessive (Liver-Gallbladder Dampness-Heat Syndrome, LGDHS) to Deficient (Liver-Kidney Deficiency Syndrome, LKYDS) via Excessive-Deficient syndrome (Liver-Depression and Spleen-Deficiency Syndrome, LDSDS). Using R package, 16 miRNAs in LGDHS/Normal, 48 miRNAs in LDSDS/LGDHS, and 16 miRNAs in LKYDS/LDSDS were identified, respectively. The miRNA-target networks show that the LDSDS was most stability and complicated. Subsequently, 4 kernel miRNAs with LGDHS-LDSDS process, and 5 kernel miRNAs with LDSDS-LKYDS process were screened. Using RT-qPCR data, p1 (hsa-miR-17-3p, -377-3p, -410-3p and -495) and p2 miRNA panel (hsa-miR-377-3p, -410-3p, -27a-3p, 149-5p and 940) were identified by Logistic Regression Model, which clearly improve the accuracy of TCM syndrome classification. The rebuilt miRNA-target network shows that the LDSDS is a critical point and might determine the evolution directions of HBC TCM syndrome. This study suggests that the identified kernel miRNAs act as potential biomarkers and benefit to evaluate the evolution tendency of HBC TCM syndromes.
Subject(s)
Biomarkers/analysis , Gene Expression Regulation , Hepatitis B/complications , Liver Cirrhosis/pathology , Medicine, Chinese Traditional/methods , MicroRNAs/metabolism , Adult , China , Female , Gene Expression Profiling , Humans , Male , Middle Aged , Real-Time Polymerase Chain Reaction , Reverse Transcriptase Polymerase Chain ReactionABSTRACT
Fuzheng-Huayu (FZHY) formula has been found to have a satisfactory effect on hepatitis B-caused cirrhosis (HBC) treatment. However, the efficacy evaluation of FZHY is often challenging. In this study, a randomized, double-blind and placebo-controlled trial was used to evaluate the therapeutic efficacy of FZHY in HBC treatment. In the trial, 35 medical indexes were detected, and 14 indexes had a statistically-significant difference before compared to after the trial. Importantly, the Child-Pugh score also demonstrated FZHY having therapeutic efficacy. Furthermore, the microRNA (miRNA) profiles of 12 serum samples were detected in FZHY groups, and 112 differential-expressed (DE) miRNAs were determined. Using predicted miRNA targets, 13 kernel miRNAs were identified from the established miRNA-target network. Subsequently, quantitative Real-time Polymerase Chain Reaction (qRT-PCR) was used to validate the expression level of 13 identified miRNAs in the trials. The results showed that nine miRNAs have a statistically-significant difference before compared to after FZHY treatment. By means of a logistic regression model, a miRNA panel with hsa-miR-18a-5p, -326, -1182 and -193b-5p was established, and it can clearly improve the accuracy of the efficacy evaluation of FZHY. This study suggested that the particular miRNAs can act as potential biomarkers and obviously increase the diagnostic accuracy for drug evaluation in HBC treatment progression.
Subject(s)
Drugs, Chinese Herbal/therapeutic use , Gene Regulatory Networks , Hepatitis B/complications , Liver Cirrhosis/drug therapy , Liver Cirrhosis/etiology , MicroRNAs/genetics , Transcriptome , Biomarkers , Cluster Analysis , Computational Biology/methods , Drugs, Chinese Herbal/pharmacology , Gene Expression Profiling , Gene Expression Regulation , Humans , Liver Cirrhosis/pathology , RNA Interference , ROC Curve , Treatment OutcomeABSTRACT
ETHNOPHARMACOLOGICAL RELEVANCE: The root of Panax ginseng C.A. Meyer (Family Araliaceae) is an important medicinal plant which has been employed as a panacea for more than 2,000 years in China. It has the actions of invigorating primordial qi, recovering pulse and desertion, engendering liquid, and calming spirit. The water extract of Panax ginseng (WEG) has been used to treat kinds of central nervous system disorders, such as depression, insomnia, Alzheimer׳s disease and Parkinson׳s disease. Our previous work has demonstrated that WEG possessed antidepressant-like activities in both acute and chronic stress models of depression. Nevertheless, there are no studies on the cytoprotection and potential mechanisms of WEG on corticosterone-induced apoptosis. The present study focuses on cytoprotection against corticosterone-induced neurotoxicity in PC12 cells and its underlying molecule mechanisms of the antidepressant-like effect of WEG. MATERIALS AND METHODS: The PC12 cells were treated with 250 µmol/L corticosterone in the absence or presence of WEG for 24h, then 3-(4,5-dimethy thiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) assay, lactate dehydrogenase (LDH) detection, Hoechst33342 staining and TUNEL staining were investigated to confirm the neuroprotection of WEG. Then, mitochondrial permeability transition pore (mPTP), mitochondrial membrane potential (MMP), intracellular Ca(2+) ([Ca(2+)]i), reactive oxygen species (ROS) concentration, and the expression level of glucocorticoid receptor (GR), heat shock protein 90 (Hsp90), histone deactylase 6 (HDAC6), glucose-regulated protein 78 (GRP78), growth arrest and DNA damage inducible protein 153 (GADD153), X-box DNA-binding protein-1 (XBP-1), caspase-12, cytochrome C, inhibitor of caspase-activated deoxyribonuclease (ICAD), caspase-3 and caspase-9 were assessed by Western Blot analysis to understand the molecule mechanisms of neuroprotection of WEG. RESULTS: WEG partly reversed corticosterone-induced damage in PC12 cells, which increased cell viability, decreased LDH release, and attenuated corticosterone-induced apoptosis as compared with the corticosterone-treated group. Mechanistically, compared with the corticosterone-treated group, WEG strongly attenuated [Ca(2+)]i overload and ROS level, and restored mitochondrial function, including mPTP and MMP. Furthermore, WEG strongly up-regulated the expression of GR and HDAC6, and down-regulated the expression of Hsp90, cytochrome C, ICAD, caspase-3, caspase-9 as well as endoplasmic reticulum (ER) stress-related proteins, such as GADD153, GRP78, XBP-1, and caspase-12. CONCLUSION: WEG possessed neuroprotection against corticosterone-induced damage in PC12 cells, and the underlying molecule mechanisms was depended on the intervening of HDAC6 and HSP90 of the GR-related function proteins, and subsequent restoration of ER and mitochondria functions.
Subject(s)
Endoplasmic Reticulum Stress/drug effects , Membrane Potential, Mitochondrial/drug effects , Neuroprotective Agents/pharmacology , Panax , Plant Extracts/pharmacology , Receptors, Glucocorticoid/metabolism , Animals , Apoptosis/drug effects , Apoptosis Regulatory Proteins/metabolism , Calcium/metabolism , Caspase 3/metabolism , Caspase 9/metabolism , Corticosterone/pharmacology , Cytochromes c/metabolism , HSP90 Heat-Shock Proteins/metabolism , Histone Deacetylase 6 , Histone Deacetylases/metabolism , L-Lactate Dehydrogenase/metabolism , Mitochondrial Membrane Transport Proteins/metabolism , Mitochondrial Permeability Transition Pore , PC12 Cells , Plant Roots , Rats , Reactive Oxygen Species/metabolism , Solvents/chemistry , Water/chemistryABSTRACT
Alzheimer's disease (AD) is associated with damage to hippocampal neurons and declines in cognitive functions. The accumulation of amyloid peptides is regarded as a crucial event in the initiation of AD. The neurotoxicity induced by Aß25-35 peptides was used to screen for cytoprotective factors in vitro, and the cognitive deficits induced by the injection of Aß25-35 into the hippocampus were used to evaluate effect on learning and memory. Our previous study revealed that hydrolysate of polygalasaponins (HPS) clearly improve the cognitive deficits induced by the injection of Aß25-35 in mice, but the potential active constituent of HPS remains unclear. The purposes of this study were to separate and purify the secondary saponins of HPS, screen for neuroprotective effects of the constituents in vitro, and to evaluate the effect of cognition in vivo. Various chromatographic methods were used to separate and purify the HPS. The neuroprotective effects were examined in Aß25-35-damage-induced PC12 cells. The protective effect of tenuifolin on the cognitive impairments induced by Aß25-35 injection was assessed using the Morris water maze and step-through passive avoidance tests. Tenuifolin and fallaxsaponin A were isolated from the HPS. Tenuifolin possessed neuroprotective effects against Aß25-35-induced apoptosis in PC12 cells and significantly improved the cognitive deficits induced by the intrahippocampal injection of Aß25-35 in mice. Thus, tenuifolin is one of the active constituents of HPS against the neurotoxicity induced by Aß25-35 peptides in vitro and in vivo.
Subject(s)
Amyloid beta-Peptides , Diterpenes, Kaurane , Neuroprotective Agents , Neurotoxins , Peptide Fragments , Animals , Humans , Mice , Rats , Alzheimer Disease/drug therapy , Alzheimer Disease/etiology , Alzheimer Disease/psychology , Amyloid beta-Peptides/physiology , Diterpenes, Kaurane/isolation & purification , Diterpenes, Kaurane/pharmacology , Hippocampus/drug effects , Hippocampus/physiopathology , Hydrolysis , In Vitro Techniques , Learning/drug effects , Memory/drug effects , Models, Animal , Neuroprotective Agents/isolation & purification , Neuroprotective Agents/pharmacology , Neurotoxins/toxicity , PC12 Cells , Peptide Fragments/physiology , Phytotherapy , Saponins/chemistry , Saponins/pharmacologyABSTRACT
Learning and memory disorders arise from distinct age-associated processes, and aging animals are often used as a model of memory impairment. The root of Polygala tenuifolia has been commonly used in some Asian countries as memory enhancer and its memory improvement has been reported in various animal models. However, there is less research to verify its effect on memory functions in aged animals. Herein, the memory-enhancing effects of the crude extract of Polygala tenuifolia (EPT) on normal aged mice were assessed by Morris water maze (MWM) and step-down passive avoidance tests. In MWM tests, the impaired spatial memory of the aged mice was partly reversed by EPT (100 and 200 mg/kg; P < 0.05) as compared with the aged control mice. In step-down tests, the nonspatial memory of the aged mice was improved by EPT (100 and 200 mg/kg; P < 0.05). Additionally, EPT could increase superoxide dismutase (SOD) and catalase (CAT) activities, inhibit monoamine oxidase (MAO) and acetyl cholinesterase (AChE) activities, and decrease the levels of malondialdehyde (MDA) in the brain tissue of the aged mice. The results showed that EPT improved memory functions of the aged mice probably via its antioxidant properties and via decreasing the activities of MAO and AChE.
ABSTRACT
ETHNOPHARMACOLOGICAL RELEVANCE: The root of Bupleurum yinchowense Shan et Y. Li, a well-known medicinal plant in China, was originally documented in the "Shennong's Herbal", which is the oldest Chinese materia medica monographs. It has the action of soothing liver and relieving constraint for improving symptoms of emotional instability such as depression, anxiety and phobia. The in vivo experiment of our previous study has showed an efficacy of Total Saikosaponins (TSS) from Bupleurum yinchowense in acute stress and chronic unpredictable mild stress models. Nevertheless, there are no studies on the cytoprotection and potential mechanisms of TSS on corticosterone-induced apoptosis in PC12 cells. The present study focuses on cytoprotection against corticosterone-induced neurotoxicity in PC12 cells and its underlying molecule mechanisms of the antidepressant-like effect of TSS. MATERIALS AND METHODS: The PC12 cells were treated with 250 µM corticosterone in the absence or presence of different concentrations of TSS for 24 h, then the cell viability, lactate dehydrogenase (LDH) release, Hoechst 33342 and propidium iodide (PI) double staining and the DNA fragmentation of the apoptotic PC12 cells were determined. The mitochondrial permeability transition pore (mPTP), mitochondrial membrane potential (MMP), intracellular Ca(2+) ([Ca(2+)]i) concentration and western blot analysis of caspase-3, glucose-regulated protein 78 (GRP78), growth arrest and DNA damage inducible proteins 153 (GADD-153), X-box DNA-binding protein-1 (XBP-1), Bax, Bcl-2 were investigated. RESULTS: Pretreatment of PC12 cells with TSS (3.125, 6.25, 12.5, 25 µg/ml) partly reversed corticosterone-induced neurotoxicity in a dose dependent manner. TSS (25 =g/ml) reversed the increase of dead cells in the Hoechst 33342 stain, the accumulation in LDH leakage and the number of TUNEL positive cells induced by corticosterone to PC12 cells. Moreover, the cytoprotection of TSS was proved to be associated with the homeostasis of intracellular Ca(2+), the stabilization of ER stress via the down-regulation of GRP78, GADD-153, XBP-1, and the restoration of mitochondrial function, which included mPTP, MMP and caspase-3 activity. Furthermore, TSS (25 µg/ml) markedly ameliorated up-regulation of Bax and down-regulation of Bcl-2 in corticosterone-induced PC12 cells. CONCLUSION: The result depicted that antidepressant-like effect of TSS in vivo may be associated with the cytoprotection of neuron, and the neuroprotective mechanisms were correlated with inhibiting the ER stress and the mitochondrial apoptotic pathways.
Subject(s)
Bupleurum , Neuroprotective Agents/pharmacology , Oleanolic Acid/analogs & derivatives , Saponins/pharmacology , Animals , Apoptosis/drug effects , Calcium/metabolism , Caspase 3/metabolism , Cell Survival/drug effects , Corticosterone , Endoplasmic Reticulum Stress/drug effects , L-Lactate Dehydrogenase/metabolism , Membrane Potential, Mitochondrial/drug effects , Mitochondria/drug effects , Oleanolic Acid/pharmacology , PC12 Cells , Rats , Sincalide/metabolismABSTRACT
Congenital hypothyroidism (CH) can lead to irreversible central nervous system (CNS) damage. However, the pathogenesis of the developmental brain disorders caused by CH has not been completely elucidated. ARPC5 and CRMP2 are closely associated with neurite outgrowth in brain development. Thus, the aim of the present study was to determine whether CRMP2B and ARPC5 expression is altered in the developing cerebral cortex of rats with CH. Control rats and rats with hypothyroidism were sacrificed at birth and at 15 days postpartum. We performed qRT-PCR to detect differences in the crmp2B and arpc5 mRNA expression in the right half of the frontal cortex of these rats. Western blotting was then used to detect differences in CRMP2B and ARPC5 protein expression. Furthermore, immunohistochemical analysis was performed on the left half of the frontal cortex to detect abnormal localization of CRMP2B and ARPC5. Results showed increased expression of the nuclear short isoform of CRMP2B and decreased expression of full-length CRMP2B and ARPC5 in cortical neurons of rats with hypothyroidism. These findings demonstrate that reduced levels of thyroid hormones can inhibit the expression of full-length CRMP2B and ARPC5 and promote nuclear transformation of the short isoform of CRMP2B. CRMP2B and ARPC5 may participate in CNS injury mediated by hypothyroidism by inducing neurite outgrowth inhibition and cytoskeletal protein disorganization.
Subject(s)
Actin-Related Protein 2-3 Complex/metabolism , Congenital Hypothyroidism/metabolism , Frontal Lobe/growth & development , Gene Expression Regulation, Developmental/physiology , Nerve Tissue Proteins/metabolism , Thyroid Hormones/metabolism , Analysis of Variance , Animals , Blotting, Western , DNA Primers/genetics , Female , Frontal Lobe/metabolism , Intercellular Signaling Peptides and Proteins , Neurites/physiology , Rats , Rats, Wistar , Real-Time Polymerase Chain Reaction , Reverse Transcriptase Polymerase Chain ReactionABSTRACT
This study is to investigate the protective effect of longistyline A against corticosterone-induced neurotoxicity in PC12 cells. While PC12 cells were exposed to 100 micromol x L(-1) corticosterone for 48 h, cell survival rate was reduced and lactate dehydrogenase (LDH) release increased. In parallel, corticosterone caused significant elevations of DNA fragmentation, [Ca2+]i and caspase-3 activity. However, when the PC12 cells were incubated with longistyline A (4.0, 8.0 and 16.0 micromol x L(-1)) in the presence of 100 micromol x L(-1) corticosterone for 48 h, the effects were evidently alleviated, but dose-dependent manner was not obvious. In summary, longistyline A could generate a neuroprotective effect against corticosterone-induced neurotoxicity in PC12 cells possibly by decreasing [Ca2+]i and caspase-3 activity.
Subject(s)
Calcium/metabolism , Caspase 3/metabolism , Cell Survival/drug effects , Neuroprotective Agents/pharmacology , Phenols/pharmacology , Animals , Cajanus/chemistry , Corticosterone/toxicity , DNA Fragmentation/drug effects , L-Lactate Dehydrogenase/metabolism , Molecular Structure , Neuroprotective Agents/isolation & purification , PC12 Cells , Phenols/isolation & purification , Plant Leaves/chemistry , Plants, Medicinal/chemistry , RatsABSTRACT
OBJECTIVE: To evaluate the effect of transcatheter arterial chemoembolization (TACE) with high-dose iodized oil on hepatic tumor growth and metastasis in rabbits. METHODS: Forty-eight rabbits with implanted VX2 tumor were randomly divided into control group, routine dose iodized oil TACE group and high-dose iodized oil TACE group to receive perfusion through the hepatic artery with 0.9% saline, 5 mg adriamycin with routine-dose iodized oil, and 5 mg adriamycin with high-dose iodized oil, respectively. The tumor volume, tumor necrosis, intrahepatic and lung metastasis were examined 2 weeks after TACE. RESULTS: No significant difference was found in the tumor volume between the 3 groups before TACE (P>0.05). The rabbits receiving TACE with iodized oil, especially at the high dose, showed significantly reduced tumor volume as compared with the control group (P<0.01). TACE with high-dose iodized oil resulted in significantly increased tumor necrosis rate in comparison with the control group and TACE with a routine dose of iodized oil (P<0.05); high-dose iodized oil TACE was also associated with reduced intrahepatic and lung metastasis as compared routine dose iodized oil TACE (P<0.05). CONCLUSION: TACE with high-dose iodized oil can obviously inhibit the growth and intrahepatic and lung metastasis of transplanted VX2 liver tumor in rabbits .
Subject(s)
Chemoembolization, Therapeutic , Contrast Media/administration & dosage , Iodized Oil/administration & dosage , Liver Neoplasms, Experimental/therapy , Animals , Catheterization, Peripheral , Chemoembolization, Therapeutic/methods , Dose-Response Relationship, Drug , Drug Carriers/administration & dosage , Female , Hepatic Artery , Male , RabbitsABSTRACT
OBJECTIVE: To investigate the efficacy of different interventional therapies for primary hepatic cell cancer (HCC). METHODS: 1126 HCC patients before or after hepatectomy were treated by different kinds of interventional therapies: transcatheter arterial chemoembolization (TACE), TACE and radio-frequency ablation (RFA), Chinese traditional medicine and biotherapy after TACE or the transcatheter arterial infusion (TAI). The results of liver function, alpha-fetoprotein, imaging, color-ultrasonography and survival rate were reviewed. RESULTS: 874 patients were followed up for 2 to 63 months. The overall 1-, 3-, 5-year survival rate was 67.8% , 28.7% and 18.8%, respectively. The 1-, 3-, 5-year survival rate of patients who received TACE before hepatectomy was 74.7%, 41.4% and 36.9% ; after hepatectomy 78.9%, 40.4% and 37.5%, respectively. The response rate ( PR + NC) of TACE and RFA was 93.4%, and the 1-, 3-year survival rate was 74.5% and 36.8%, respectively, after TACE and RFA. The response rate (PR + NC) of TACE was 83.2% with 1-, 3-, 5-year survival rate of 69.3%, 21.7%, 8.4% after TACE, respectively. The response rate (PR + NC) of TAI was 27.5% with 1-, 2-year survival rate of 11. 6% and 0 after TAI. The Child grade of liver function, color-ultrasonography and alpha-fetoprotein of TACE + RFA group, TACE and TAI were compared. There was no significant difference between each above mentioned index among TACE, RFA or TACE groups. CONCLUSION: Compared with other modalities, transcatheter arterial chemoembolization (TACE) before or after hepatectomy is more effective than other interventional therapies for primary hepatocellular cancer, whereas, if combined with radiofrequency ablation (TAI), it is much more effective than TACE alone.