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1.
Article in Chinese | WPRIM (Western Pacific) | ID: wpr-981322

ABSTRACT

This paper explored the chemical constituents of Boswellia carterii by column chromatography on silica gel, Sephadex LH-20, ODS column chromatography, and semi-preparative HPLC. The structures of the compounds were identified by physicochemical properties and spectroscopic data such as infrared radiation(IR), ultra violet(UV), mass spectrometry(MS), and nuclear magnetic resonance(NMR). Seven diterpenoids were isolated and purified from n-hexane of B. carterii. The isolates were identified as(1S,3E,7E,11R,12R)-11-hydroxy-1-isopropyl-4,8,12-trimethyl-15-oxabicyclo[10.2.1]pentadeca-3,7-dien-5-one(1),(1R,3S,4R,7E,11E)-4,8,12,15,15-pentamethyl-14-oxabicyclo[11.2.1]hexadeca-7,11-dien-4-ol(2), incensole(3),(-)-(R)-nephthenol(4), euphraticanoid F(5), dilospirane B(6), and dictyotin C(7). Among them, compounds 1 and 2 were new and their absolute configurations were determined by comparison of the calculated and experimental electronic circular dichroisms(ECDs). Compounds 6 and 7 were obtained from B. carterii for the first time.


Subject(s)
Molecular Structure , Boswellia/chemistry , Diterpenes/chemistry , Mass Spectrometry
2.
Cell Death Dis ; 13(8): 751, 2022 08 30.
Article in English | MEDLINE | ID: mdl-36042202

ABSTRACT

There is a potential correlation between G-protein-coupled receptor-associated sorting protein 1 (GASP1) and breast tumorigenesis. However, its biological function and underlying molecular mechanism in breast cancer have not been clearly delineated. Here, we demonstrated that GASP1 was highly expressed in breast cancers, and patients harboring altered GASP1 showed a worse prognosis than those with wild-type GASP1. Functional studies showed that GASP1 knockout significantly suppressed malignant properties of breast cancer cells, such as inhibition of cell proliferation, colony formation, migration, invasion and xenograft tumor growth in nude mice as well as induction of G1-phase cell cycle arrest, and vice versa. Mechanistically, GASP1 inhibited proteasomal degradation of insulin-like growth factor 1 receptor (IGF1R) by competitively binding to IGF1R with ubiquitin E3 ligase MDM2, thereby activating its downstream signaling pathways such as NF-κB, PI3K/AKT, and MAPK/ERK pathways given their critical roles in breast tumorigenesis and progression. IGF1, in turn, stimulated GASP1 expression by activating the PI3K/AKT pathway, forming a vicious cycle propelling the malignant progression of breast cancer. Besides, we found that GASP1 knockout obviously improved the response of breast cancer cells to paclitaxel. Collectively, this study demonstrates that GASP1 enhances malignant behaviors of breast cancer cells and decreases their cellular response to paclitaxel by interacting with and stabilizing IGF1R, and suggests that it may serve as a valuable prognostic factor and potential therapeutic target in breast cancer.


Subject(s)
Breast Neoplasms , Insulin-Like Growth Factor I , Animals , Breast Neoplasms/drug therapy , Breast Neoplasms/genetics , Breast Neoplasms/pathology , Cell Line, Tumor , Cell Proliferation , Cell Transformation, Neoplastic , Female , Humans , Insulin-Like Growth Factor I/metabolism , Mice , Mice, Nude , Paclitaxel/pharmacology , Paclitaxel/therapeutic use , Phenotype , Phosphatidylinositol 3-Kinases/metabolism , Proto-Oncogene Proteins c-akt/metabolism , Receptor, IGF Type 1/metabolism , Signal Transduction
4.
Journal of Forensic Medicine ; (6): 308-313, 2022.
Article in English | WPRIM (Western Pacific) | ID: wpr-984121

ABSTRACT

Individual identification is one of the research hotspots in the practice of forensic science, and the judgment is usually built on the comparison of the unique biological characteristics of the individual, such as fingerprints, iris and DNA. With the dramatic increase in the number of cases related to video image investigations, there is an increasing need for the technology to identify individuals based on the macroscopic comparison of facial appearance biometrics. At present, with the introduction of computer three-dimensional (3D) modeling and 3D superimposition comparison technology, considerable progress has been made in individual identification methods based on macroscopic comparison of facial appearance biometrics. This paper reviews individual facial appearance biometric methods based on macroscopical comparison, comprehensively analyzes the advantages and limitations of different methods, and puts forward recommendations and prospects for subsequent research.


Subject(s)
Humans , Biometric Identification , Biometry/methods , Face/anatomy & histology , Forensic Sciences/methods
5.
Journal of Forensic Medicine ; (6): 254-257, 2022.
Article in English | WPRIM (Western Pacific) | ID: wpr-984117

ABSTRACT

OBJECTIVES@#To study the distribution of total phosphine in phosphine poisoning victims and summarize the characteristics of phosphine poisoning cases.@*METHODS@#The phosphine and its metabolites in the biological samples of 29 victims in 16 phosphine poisoning cases were qualified and quantified by headspace gas chromatography-mass spectrometry.@*RESULTS@#Five victims among 29 were poisoned by ingestion of aluminium phosphide and 24 by inhalation of phosphine gas. Phosphine metabolites were detected in the biological samples of 23 victims, and the concentrations of total phosphine in blood ranged 0.5-34.0 μg/mL. The total concentration of phosphine in liver tissue was up to 71.0 μg/g. Phosphine was not detected in the blood of the other six survived victims, which may be related to the small amount of phosphine exposure and the delay in blood sampling.@*CONCLUSIONS@#The total concentration of phosphine in blood and tissues caused by aluminum phosphine ingestion is higher than that caused by phosphine gas inhalation. The death cases of phosphine inhalation are characterized by long exposure time, repeated exposures and age susceptibility.


Subject(s)
Humans , Aluminum Compounds/analysis , Gas Chromatography-Mass Spectrometry , Liver/chemistry , Phosphines/analysis , Poisoning/diagnosis
6.
Article in Chinese | WPRIM (Western Pacific) | ID: wpr-1015680

ABSTRACT

Mitochondria are dynamic organelles that continuously divide and fuse. In recent years, in addition to the studies related to mitochondrial metabolism, the unique dynamics of mitochondria have gradually attracted researchers' attention. A growing body of research has revealed that mitochondrial dynamics are related to the biological behavior of tumor cells. Mitochondrial fission proteins (mitochondrial fission protein 1, FIS1) mediate the assembly of mitochondrial fission complexes and participate in the execution of mitochondrial fission. They are important proteins in the process of mitochondrial fusion and fission. However, few studies have revealed the expression and role of FIS1 in human cervical cancer. In this study, the expression level of FIS1 in human cervical cancer tissues and paracancer tissues were compared. The results showed that the level of FIS1 mRNA in human cervical cancer tissues was significantly lower than that in paracancer tissues (P<0. 01). Further KEGG pathway and GO Term-BP pathway analysis showed that the differential genes are mainly related to mitochondrial biological functions. Subsequently, HeLa cells with overexpressed FIS1 were investigated for their proliferation, migration, mitochondrial fission and ROS levels. The experimental results showed that FIS1 overexpression decreased HeLa cell proliferation and migration ability, enhanced mitochondrial fission and higher ROS levels. In conclusion, the expression of FIS1 in human cervical cancer cells was attenuated, while overexpression of FIS1 resulted in a series of abnormal biological functions in human cervical cancer cells. Further studies can be carried out to investigate the role of FIS1 in the treatment of human cervical cancer.

7.
Breast ; 60: 287-294, 2021 Dec.
Article in English | MEDLINE | ID: mdl-34844175

ABSTRACT

BACKGROUND: Radiotherapy after breast-conserving surgery (BCS) is not always necessary in older women staged T1N0M0 with low-risk invasive breast cancer, but few studies have concluded the detailed tumor size as a reference for avoiding radiotherapy. The study was conducted to explore and identify the optimal cutoff tumor size. METHODS: The study population was from the Surveillance, Epidemiology, and End Results (SEER) database in 2010-2016. Propensity score matching was used to balance the confounders between groups. Predictors associated with survival were analyzed by Kaplan-Meier, X-tile, Cox proportional hazards model and competing risk model. RESULTS: A total of 52049 women and 3846 deaths were included in the cohort with a median follow-up of 34 months. Based on the cutoff value determined by X-tile analysis, the study population were divided into small tumor group (≤14 mm in diameter) and large tumor group (>14 mm in diameter). Small tumors and radiotherapy were correlated with better breast cancer-specific survival (BCSS). In subgroup analysis, the absolute benefit of BCSS in 6 years attributed to radiotherapy was only 0.90% (RT vs. non- RT:98.77% vs. 97.87%) for patients with small tumors but up to 3.33% (RT vs. non- RT:97.10% vs. 93.77%) for those with large tumors. CONCLUSION: Small tumors and adjuvant radiotherapy were associated with improved long-term prognosis, and 14 mm in diameter was the cutoff tumor size of omitting radiotherapy for patients aged 65 or older with T1N0M0 stage, ER+ and HER2-breast carcinoma after BCS.


Subject(s)
Breast Neoplasms , Mastectomy, Segmental , Aged , Breast/pathology , Breast Neoplasms/pathology , Breast Neoplasms/radiotherapy , Breast Neoplasms/surgery , Female , Humans , Neoplasm Staging , Radiotherapy, Adjuvant , SEER Program
8.
Biomacromolecules ; 22(8): 3590-3600, 2021 08 09.
Article in English | MEDLINE | ID: mdl-34286578

ABSTRACT

One of the biggest challenges of the protein delivery system is to realize stable and high protein encapsulation efficiency in blood circulation and rapid release of protein in the targeted tumor cells. To overcome these hurdles, we fabricated enzyme-responsive photo-cross-linked nanogels (EPNGs) through UV-triggered chemical cross-linking of cinnamyloxy groups in the side chain of PEGylation hyaluronic acid (HA) for CD44-targeted transport of cytochrome c (CC). The EPNGs showed high loading efficiency and excellent stability in different biological media. Notably, CC leakage effectively suppressed under physiological conditions but accelerated release in the presence of hyaluronidase, an overexpressed enzyme in tumor cells. Moreover, thiazolylblue tetrazolium bromide (MTT) results indicated that the vacant EPNGs showed excellent nontoxicity, while CC-loaded EPNGs exhibited higher killing efficiency to CD44-positive A549 cells than to CD44-negative HepG2 cells and free CC. Confocal images confirmed that CC-loaded EPNGs could effectively be internalized by CD44-mediated endocytosis pathway and rapidly escape from the endo/lysosomal compartment. Human lung tumor-bearing mice imaging assays further revealed that CC-loaded EPNGs actively target tumor locations. Remarkably, CC-loaded EPNGs also exhibited enhanced antitumor activity with negligible systemic toxicity. These results implied that these EPNGs have appeared as stable and promising nanocarriers for tumor-targeting protein delivery.


Subject(s)
Nanoparticles , A549 Cells , Animals , Cell Line, Tumor , Humans , Hyaluronic Acid , Mice , Nanogels
9.
Journal of Forensic Medicine ; (6): 378-381, 2021.
Article in English | WPRIM (Western Pacific) | ID: wpr-985228

ABSTRACT

Objective To establish a method for determination of the azide ions in blood by gas chromatography-mass spectrometry (GC-MS) following pentafluorobenzyl derivatization. Methods A blood sample of 0.2 mL was placed into a 10 mL glass test tube, and the internal standard sodium cyanide, derivatization reagent pentafluorobenzyl bromide and catalyst tetradecyl benzyl dimethyl ammonium chloride were added in turn. After vortex mixing, the mixture was heated with low-power microwave for 3 min. After centrifugation, the organic phase was taken for GC-MS analysis. Results The azide ions in blood had a good linear relationship in the mass concentration range of 0.5 to 20 μg/mL. The lowest detection limit was 0.25 μg/mL and the relative recovery was 91.36%-94.58%. The method was successfully applied to a case of death from sodium azide poisoning. The mass concentration of azide ions in the blood of the dead was 11.11 μg/mL. Conclusion The method developed in this paper has strong specificity and is easy to operate, which is suitable for the rapid detection of azide ions in blood.


Subject(s)
Humans , Azides , Gas Chromatography-Mass Spectrometry , Ions
10.
FASEB J ; 34(8): 10860-10870, 2020 08.
Article in English | MEDLINE | ID: mdl-32592239

ABSTRACT

The tumor microenvironment (TME) is a crucial factor in cancer progression. In breast cancer, cancer-associated fibroblasts (CAFs) and the derived stromal components have been recognized as comprising the majority of the pathological structure of the TME. In this study, we show that metformin (Met), a diabetes drug, transforms CAFs in the TME. Met disrupts tumor-stromal cross talk by preventing breast cancer cell transforming growth factor-ß (TGF-ß) signaling and the production of stromal-derived factor-1 (SDF-1) and interleukin-8 (IL-8) by CAFs. The suppression of bidirectional signaling between tumor cells and CAFs by Met is attributed to increased phospho-AMP kinase (p-AMPK) levels. By upregulating p-AMPK in CAFs, Met induces prolyl hydroxylases (PHDs), leading to the degradation of hypoxia-inducible factor-1α (HIF-1α) in CAFs. Moreover, interruption of HIF-1α-driven SDF-1 signaling in CAFs by Met leads to decreased breast cancer cell invasion. These findings suggest that Met may be used to target tumor-promoting signaling between CAFs and breast cancer cells in the TME.


Subject(s)
Breast Neoplasms/drug therapy , Breast Neoplasms/metabolism , Cancer-Associated Fibroblasts/drug effects , Cancer-Associated Fibroblasts/metabolism , Hypoxia-Inducible Factor 1, alpha Subunit/metabolism , Metformin/pharmacology , Adenylate Kinase/metabolism , Breast Neoplasms/pathology , Cancer-Associated Fibroblasts/pathology , Cell Line, Tumor , Chemokine CXCL12/metabolism , Female , Humans , Interleukin-8/metabolism , MCF-7 Cells , Neoplasm Invasiveness/pathology , Prolyl Hydroxylases/metabolism , Signal Transduction/drug effects , Transforming Growth Factor beta/metabolism , Tumor Microenvironment/drug effects , Up-Regulation/drug effects
11.
Preprint in English | medRxiv | ID: ppmedrxiv-20115196

ABSTRACT

The COVID-19 pandemic has brought an unprecedented crisis to the global health sector1. When recovering COVID-19 patients are discharged in accordance with throat or nasal swab protocols using reverse transcription polymerase chain reaction (RT-PCR), the potential risk of re-introducing the infection source to humans and the environment must be resolved2,3,4. Here we show that 20% of COVID-19 patients, who were ready for a hospital discharge based on current guidelines, had SARS-CoV-2 in their exhaled breath ([~]105 RNA copies/m3). They were estimated to emit about 1400 RNA copies into the air per minute. Although fewer surface swabs (1.3%, N=318) tested positive, medical equipment frequently contacted by healthcare workers and the work shift floor were contaminated by SARS-CoV-2 in four hospitals in Wuhan. All air samples (N=44) appeared negative likely due to the dilution or inactivation through natural ventilation (1.6-3.3 m/s) and applied disinfection. Despite the low risk of cross environmental contamination in the studied hospitals, there is a critical need for strengthening the hospital discharge standards in preventing re-emergence of COVID-19 spread.

12.
J Vis Exp ; (159)2020 05 01.
Article in English | MEDLINE | ID: mdl-32420992

ABSTRACT

Stereotaxic injection has been widely used for direct delivery of compounds or viruses to targeted brain areas in rodents. Direct targeting of serotonergic neurons in the dorsal raphe nucleus (DRN) can cause excessive bleeding and animal death, due to its location below the superior sagittal sinus (SSS). This protocol describes the generation of a DRN serotonergic neuron-lesioned mouse model (>90% survival rate) with stable loss of >70% 5-HT-positive cells in the DRN. The lesion is induced by stereotaxic injection of a selective serotonergic neurotoxin 5,7-dihydroxytryptamine (5,7-DHT) into the DRN using an angled approach (30° in the anterior/posterior direction) to avoid injury to the SSS. DRN serotonergic neuron-lesioned mice display anxiety-associated behavior alterations, which helps to confirm success of the DRN lesion surgery. This method is used here for DRN lesions, but it can also be used for other stereotaxic injections that require angular injections to avoid midline structures. This DRN serotonergic neuron-lesioned mouse model provides a valuable tool for understanding the role of serotonergic neurons in the pathogenesis of psychiatric disorders, such as generalized anxiety disorder and major depressive disorder.


Subject(s)
5,7-Dihydroxytryptamine/administration & dosage , Dorsal Raphe Nucleus/drug effects , Serotonergic Neurons/physiology , Stereotaxic Techniques , 5,7-Dihydroxytryptamine/pharmacology , Animals , Behavior, Animal/drug effects , Disease Models, Animal , Male , Mice, Inbred C57BL
13.
Int J Radiat Oncol Biol Phys ; 107(3): 499-511, 2020 07 01.
Article in English | MEDLINE | ID: mdl-32179132

ABSTRACT

PURPOSE: To evaluate the effect of hyperthermia combined with concurrent radiochemotherapy (RCT) and treatment-related toxicity in patients with cervical cancer (CC) stage IB-IV. METHODS AND MATERIALS: This study was conducted between 2009 and 2013 in patients with International Federation of Gynecology and Obstetrics (FIGO) stage IB-IV CC. The patients were randomly assigned into 2 treatment groups: RCT and RCT plus hyperthermia (RCHT). Five-year survival, treatment-related toxicity, and other prognostic factors were evaluated. RESULTS: Three hundred seventy-three patients completed treatment and were analyzed by per-protocol (PP) analysis. The 5-year overall survival (OS) in the RCHT group (81.9%) was better than that in RCT group (72.3%), and the log-rank test showed a statistically significant difference between the 2 groups (P = .040). Univariate and multivariate Cox regression analysis for 5-year OS showed a statistically significant difference (P = .043, P = .045, respectively). The 5-year local relapse-free survival in RCHT (86.8%) was also better than that in RCT (82.7%), but the difference was not significant. Acute or late toxicity was not significantly different between the 2 groups. Advanced clinical stage (FIGO) and larger tumor size showed higher risk of death and a relatively poor prognosis in univariate and multivariate analysis. CONCLUSIONS: The study confirmed that hyperthermia combined with RCT yielded a better 5-year OS in CC. Acute and late toxicity was similar between the RCT and RCHT groups. Clinical stage (FIGO) and tumor size were independent prognostic factors in CC.


Subject(s)
Chemoradiotherapy , Hyperthermia, Induced , Uterine Cervical Neoplasms/therapy , Adult , Aged , Female , Humans , Middle Aged , Survival Analysis , Uterine Cervical Neoplasms/pathology
14.
Article in Chinese | WPRIM (Western Pacific) | ID: wpr-849700

ABSTRACT

Lipodermatosclerosis (LDS) is a serious skin change associated with the progression of chronic venous insufficiency (CVI) of the lower extremities, and can be clinically divided into acute phase, subacute phase and chronic phase. The disease is common in middle-aged women, prone to occur in the lower leg 1/3, clinical manifestations of the skin flake erythema, induration, pigmentation, skin rough and thickening. The patients often suffer from secondary infection after scratching due to pruritus. The severe ones can form refractory ulcer or even cause skin necrosis, and may be canceration. At present, domestic reports on LDS are less, the clinical manifestations, etiology, pathogenesis and treatment of the LDS are reviewed in present paper, in order to strengthen the understanding of LDS and provide the evidence for clinical diagnosis and treatment of LDS.

15.
Acta Pharmaceutica Sinica ; (12): 2595-2605, 2020.
Article in Chinese | WPRIM (Western Pacific) | ID: wpr-837507

ABSTRACT

In recent years, layer-by-layer self-assembly (LbL) has developed rapidly. It has been widely used in various industries such as medicine and metallurgy because of its simplicity, flexibility and controllability. In the study of drug delivery system, hollow microcapsules constructed by LbL method as drug carrier have great advantages in drug release, circulation in vivo and bioavailability, providing a technical platform for targeted drug release. In this paper, we summarize the types of film-forming materials and the driving force used in LbL technology, the way of loading drug into hollow micro capsule, and the variety of loaded drugs. We focus on the release mechanism, its evaluation and safety evaluation of self-assembled film as drug carrier in vivo and in vitro. The review shows the great application prospect of LbL technology in the field of drug delivery.

16.
Onco Targets Ther ; 12: 3919-3931, 2019.
Article in English | MEDLINE | ID: mdl-31213826

ABSTRACT

Background: Breast cancer is one of the foremost threats to female health nowadays. Tamoxifen, an antagonist of estrogen receptor-α (ERα), is the first choice for endocrine-dependent breast cancer (ERα-positive breast cancer) treatment. However, ERα has an important function in the normal physical regulation of estrogen, and current oral administration of tamoxifen has potential side effects on normal endocrine secretion. In the present work, we aim to develop novel approaches to increase the antitumor effect of tamoxifen on breast cancer cells and decrease the potential side effects in the human body during treatment. Methods: A temperature-sensitive phase-change hydrogel for tamoxifen (Tam-Gel) was generated. After establishing subcutaneous tumors formed by MCF-7, an ERα-positive breast cancer cell line, in nude mice, an intratumoral injection of Tam-Gel was performed to examine whether Tam-Gel facilitated the slow-release or antitumor effect of tamoxifen. A metastatic breast cancer model was established using the intrahepatic growth of MCF-7 cells in immunodeficient rats. Results: Tam-Gel can transform from liquid to hydrogel at room temperature. An intratumoral injection of Tam-Gel facilitated the slow-release or antitumor effect of tamoxifen. Once Tam-Gel, but not Tam-Sol, was administered by intratumoral injection, it significantly decreased the uptake of radionuclide probes (18F-fluoroestradiol or 18F-fluorodeoxyglucose) by cells in rats' livers and the intrahepatic growth of MCF-7 cells in rats' livers. Conclusion: A novel slow-release system was successfully prepared to facilitate the long-term release of tamoxifen in breast cancer tissues, and achieved an antitumor effect in the long term.

17.
J Cancer Res Clin Oncol ; 145(2): 411-427, 2019 Feb.
Article in English | MEDLINE | ID: mdl-30483898

ABSTRACT

The pre-metastatic niche has been shown to play a critical role in tumor metastasis, and its formation is closely related to the tumor microenvironment. However, the underlying molecular mechanisms remain unclear. In the present study, we successfully established a mouse model of lung metastasis using luciferase-expressing MDA-MB-435s cells. In this model, recruitment of vascular endothelial growth factor receptor-1 (VEGFR1)+CD133+ hematopoietic progenitor cells (HPCs) was gradually increased in lung but gradually decreased after the formation of tumor colonies in lung. We also established a highly metastatic MDA-MB-435s (MDA-MB-435s-HM) cell line from the mouse model. Changes in protein profiles in different culture conditions were investigated by protein microarray analysis. The levels of CXC chemokine ligand 16, interleukin (IL)-2Rα, IL-2Rγ, matrix metalloproteinase (MMP)-1, MMP-9, platelet-derived growth factor receptor (PDGFR)-α, stromal cell-derived factor (SDF)-1α, transforming growth factor (TGF)-ß, platelet endothelial cell adhesion molecule (PECAM)-1 and vascular endothelial (VE)-cadherin were significantly greater (> fivefold) in the culture medium from MDA-MB-435s-HM cells than in that from MDA-MB-435s cells. Moreover, the levels of MMP-9, PDGFR-α, and PECAM-1 were significantly greater in the co-culture medium of MDA-MB-435s-HM cells and CD133+ HPCs than in that from MDA-MB-435s-HM cells. Differentially expressed proteins were validated by enzyme-linked immunosorbent assay, and expression of their transcripts was confirmed by quantitative real-time polymerase chain reaction. Moreover, inhibition of MMP-9, PDGFR-α, and PECAM-1 by their specific inhibitors or antibodies significantly decreased cell migration, delayed lung metastasis, and decreased recruitment of VEGFR1+CD133+ HPCs into lung. Intra-hepatic growth of HPCs enhanced the invasive growth of MDA-MB-435s-HM cells in the liver. Our data indicate that VEGFR1+CD133+ HPCs contribute to lung metastasis.


Subject(s)
Biomarkers, Tumor/metabolism , Breast Neoplasms/pathology , Hematopoietic Stem Cells , Lung Neoplasms/secondary , Vascular Endothelial Growth Factor Receptor-1/metabolism , Animals , Apoptosis , Breast Neoplasms/drug therapy , Breast Neoplasms/metabolism , Cell Movement , Cell Proliferation , Female , Humans , Lung Neoplasms/drug therapy , Lung Neoplasms/metabolism , Mice , Mice, Inbred BALB C , Mice, Nude , Neoplasm Invasiveness , Protein Array Analysis , Small Molecule Libraries/pharmacology , Tumor Cells, Cultured , Xenograft Model Antitumor Assays
18.
Article in Chinese | WPRIM (Western Pacific) | ID: wpr-776052

ABSTRACT

Objective To investigate the changes of serum melatonin(MLT)and glutathione(GSH)levels in patients with Parkinson's disease(PD)and explore their relationships with disease severity,cognitive dysfunction,and sleep disorders. Methods Totally 50 PD patients treated in our center from September 2017 to February 2018 were enrolled as the PD group,and 50 healthy controls matched with age and sex as the control group.The improved Hoehn and Yahr scale was used to assess the severity of PD.The Montreal Cognitive Assessment Scale was used to assess the cognitive function and Pittsburgh's Sleep Quality Index was used to detect the patient's sleep.The serum levels of MLT and GSH were detected by enzyme-linked immunosorbent assay and the results were compared. Results Serum MLT level in the PD group was significantly higher than that in the control group [(84.12±6.58)pg/ml vs.(46.29±9.73)pg/ml,P=0.000],and serum GSH level was significantly lower than that in the control group [(21.07±12.05)μmol/L vs.(77.73±39.90)μmol/L,P=0.000].There was a positive correlation between serum MLT level and H-Y grade(r=0.537,P=0.000),and there was a negative correlation between serum GSH level and H-Y grade(r=-0.596,P=0.000).Serum MLT was negatively correlated with GSH level in PD patients(r=-0.842,P=0.000).The MLT level in PD patients with sleep disorders was significantly higher than in those without sleep disorders [(85.79±6.45)pg/ml vs.(78.84±3.54)pg/ml,P=0.001];the level of GSH in PD patients with cognitive dysfunction was significant lower than in the non-cognitive dysfunction group [(17.47±10.67)μmol/L vs.(26.09±12.23)μmol/L,P=0.011]. Conclusions Serum MLT level increases and GSH level decreases in PD patients.Both MLT and GSH are correlated with PD severity,and there is a negative correlation between MLT and GSH.In addition,PD patients with sleep disorders have higher MLT level and those with cognitive impairment tend to have lower GSH level.


Subject(s)
Humans , Case-Control Studies , Cognitive Dysfunction , Glutathione , Blood , Melatonin , Blood , Oxidative Stress , Parkinson Disease , Blood , Sleep Wake Disorders
19.
Onco Targets Ther ; 11: 7733-7743, 2018.
Article in English | MEDLINE | ID: mdl-30464522

ABSTRACT

BACKGROUND: Urokinase plasminogen activator (uPA) promotes the in vivo invasive growth of HCC cells by cleaving and activating matrix metalloproteinases (MMPs) to induce the destruction of the extracellular matrix of triple-negative breast cancer (TNBC) cells. The identification of microRNAs that target uPA and decrease uPA expression would be useful for attenuating the in vivo invasive growth of TNBC cells. MATERIALS AND METHODS: MicroRNA-645 (miR-645) was identified using an online tool (miRDB) as potentially targeting uPA; miR-645 inhibition of uPA was confirmed by western blot experiments. The effects of miR-645 on the in vivo invasive growth of TNBC cells were examined using an intrahepatic tumor model in nude mice, and the miR-645 mechanism of action was explored with MMP cleaving experiments. RESULTS: Through virtual screening, we discovered that miR-645 potentially targeted the uPA 3' untranslated region. This targeting was confirmed by western blot experiments and miR-645 lentiviral particle (LV-645) transduction that inhibited uPA expression in MDA-MB-231 TNBC cells. The LV-645 inhibition of uPA led to the decreased invasive growth of TNBC cells in nude mice. The mechanism data indicated that the uPA inhibition resulted in a decreased cleaving of the pro-MMP-9 protein. CONCLUSION: Targeting uPA with miR-645 decreased the in vivo invasive growth of TNBC cells. These results suggest that miR-645 may represent a promising treatment strategy for TNBC.

20.
Curr Pharm Des ; 24(15): 1682-1688, 2018.
Article in English | MEDLINE | ID: mdl-29766795

ABSTRACT

INTRODUCTION: Although a great many strategies have been proposed for tumor-targeted chemotherapy, current delivery methods of anticancer drugs present limited success with inevitable systemic toxicity. The aim of this study was to develop a new kind of theranostic carrier for targeted tumor therapy. METHODS: Prior to prepare CHC-PFP-DOX, carboxymethyl-hexanoyl chitosan (CHC) was synthesized by acylation of carboxymethyl chitosan. To develop CHC-PFP, perfluoropentane (PFP), an ultrasound gas precursor, was simultaneously encapsulated into the hydrophobic inner cores of pre-formulated CHC micelle in aqueous phase via using the oil in water (O/W) emulsion method. The size distribution and surface charges of these nanodroplets were measured and the morphology was observed by transmission electron microscopy (TEM). For ultrasound imaging application, in vitro model was established to evaluate the imaging of CHC-PFP-DOX under different concentration and mechanical index. After that, the anti-tumor effect of ultrasound combined with CHC-PFPDOX on ovarian cancer cells was investigated. RESULTS: The resulting CHC-PFP-DOX had a nano-sized particle structure, with hydrophobic anticancer DOX/PFP inner cores and a hydrophilic carboxymethyl chitosan polymer outer shell. The favorable nano-scaled size offers the potential to extravagate from veins and accumulate in tumor tissues via enhanced permeation and retention (EPR) effect. Additionally, CHC-PFP-DOX showed the ability to serve as ultrasound imaging agent at body temperature. Notably, it exhibited an ultrasound-triggered drug release profile through the external ultrasound irradiation. Further study demonstrated that ultrasound combined with CHC-PFP-DOX can improve the killing effect of chemotherapy for tumor. CONCLUSION: CHC-PFP-DOX holds great promise in simultaneous cancer-targeting ultrasound imaging and ultrasound- mediated delivery for cancer chemotherapy.


Subject(s)
Antibiotics, Antineoplastic/pharmacology , Chitosan/analogs & derivatives , Doxorubicin/pharmacology , Drug Delivery Systems , Nanoparticles/chemistry , Ovarian Neoplasms/drug therapy , Ultrasonography , Antibiotics, Antineoplastic/chemistry , Cell Proliferation/drug effects , Cells, Cultured , Chitosan/chemistry , Doxorubicin/chemistry , Drug Screening Assays, Antitumor , Female , Humans , Micelles , Ovarian Neoplasms/pathology , Particle Size , Surface Properties
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