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1.
J Clin Ultrasound ; 52(3): 295-304, 2024.
Article in English | MEDLINE | ID: mdl-38143429

ABSTRACT

PURPOSE: This study explored the correlation between inflammatory markers and ulcerative plaques based on carotid doppler ultrasound (CDU) in individuals with acute ischemic stroke (AIS). METHODS: A total of 202 cases diagnosed with AIS associated with atherosclerotic plaque (AP) in the carotid artery were enrolled in this research. Collecting clinical baseline data, laboratory data (such as the complete blood count) and imaging data (CDU and Brain magnetic resonance imaging [MRI]). Then the correlation between Systemic immune-inflammation index (SII, SII = P N/L, where P, N, and L were the peripheral blood platelet, neutrophil and lymphocyte counts, respectively), the shape and position of AP, the degree of carotid artery stenosis, and the presence of ulcerative plaques. Cutoff values were determined accordingly. RESULTS: SII and high sensitivity CRP (hs-CRP) were independent risk factors for the presence of vulnerable carotid plaques. SII, type A plaque, plaque above carotid bifurcation, and severe carotid stenosis were independent risk factors for the presence of ulcerative plaque. The AUC value, the sensitivity, specificity, the best cutoff value of SII in predicting the presence of ulcerative plaque was 0.895, 93.3%, 89.2%, and 537.4 (109 /L), respectively. CONCLUSION: SII at admission was found to be independently associated with the presence of AIS with vulnerable plaque, especially ulcerative plaques. Moreover, plaque ulceration was more likely to form when the area of higher plaque thickness was located in the upstream arterial wall of maximum plaque thickness (WTmax), plaque was above the carotid bifurcation and severe carotid stenosis.


Subject(s)
Carotid Stenosis , Ischemic Stroke , Plaque, Atherosclerotic , Stroke , Humans , Plaque, Atherosclerotic/complications , Plaque, Atherosclerotic/diagnostic imaging , Plaque, Atherosclerotic/pathology , Carotid Stenosis/complications , Carotid Stenosis/diagnostic imaging , Ischemic Stroke/complications , Ischemic Stroke/diagnostic imaging , Ischemic Stroke/pathology , Carotid Arteries/pathology , Inflammation/diagnostic imaging , Inflammation/complications , Inflammation/pathology , Stroke/complications , Stroke/diagnostic imaging
2.
J Control Release ; 364: 23-36, 2023 12.
Article in English | MEDLINE | ID: mdl-37863358

ABSTRACT

PEGylated cholesterol-containing liposomes (Chol-PEG-lipo) have been widely used as a drug carrier for their good stealth property in blood circulation where cholesterol maintains the stability of the liposomal lipid bilayer and PEGylation endows liposomes with long circulation capability. However, cholesterol-related disadvantages and the accelerated blood clearance (ABC) phenomenon caused by PEGylation greatly limit the application of conventional stealth liposomes in clinic. Herein, ginsenoside Rg3 was selected to substitute cholesterol and PEG for liposomes preparation (Rg3-lipo). Rg3 was proved with similar liposomal membrane regulation ability to cholesterol and comparable long circulation effect to PEG. In addition, repeated administrations of Chol-PEG-lipo and Rg3-lipo were performed. The circulation time of the second dose of Chol-PEG-lipo was substantially reduced accompanied by a greatly increased accumulation in the liver due to the induction of anti-PEG IgM and the subsequent activated complement system. In contrast, no significantly increased level of relative plasma cells, IgM secretion and the complement activation in blood circulation was observed after the second injection of Rg3-lipo. As a result, Rg3-lipo showed great stealth property without ABC phenomenon. Therefore, developing liposomes utilizing Rg3 instead of PEG and cholesterol presents a promising strategy to prolong the blood circulation time of liposomes without triggering the ABC phenomenon and activated immune responses.


Subject(s)
Liposomes , Polyethylene Glycols , Rats , Animals , Rats, Wistar , Immunoglobulin M , Cholesterol
3.
Poult Sci ; 102(3): 102298, 2023 Mar.
Article in English | MEDLINE | ID: mdl-36638759

ABSTRACT

This study aimed to assess the effect of inbreeding on production traits using a long-term closed-line population recorded for residual feed intake (RFI). The study first used data from a previously reported population to determine the appropriate period of divergent selection for RFI. The results showed that RFI had similar moderate heritability estimates (0.28-0.34) during the fast-growing period (7-12 wk), and RFI at 7 to 10 wk had the highest heritability (0.34). Therefore, divergent selection was performed in a Chinese broiler population for RFI at 7 to 10 wk; the total sample size from generations zero (G0) to 13 was 9050. The divergence between the 2 lines increased steadily throughout generations, resulting in G13 with average RFI values of 304.55 in high RFI (HRFI) males, -160.31 in low RFI (LRFI) males, 296.30 in HRFI females and -157.55 in LRFI females. The feed intake (FI) and feed conversion ratio were almost higher in HRFI broilers than in LRFI broilers, and the magnitude of the difference in FI increased from approximately 4% for both sexes in G1 to approximately 33% in G13. Body weight gain was irregular from G1 to G13 and higher in LRFI broilers than in HRFI broilers after G10. Indeed, the HRFI broilers consumed more food, but they were lighter than LRFI broilers. In G13, LRFI males had heavier slaughter weight, longer cecum length, more white blood cells (WBC), red blood cells (RBC) and hemoglobin (HGB), but triglycerides, lower dressed percentage, percentage of half eviscerated yield, and eviscerated yield than HRFI males. LRFI females had a higher percentage of breast muscle and gizzard yield, longer cecum length, and more WBCs, RBCs and HGB but less abdominal fat and serum total cholesterol than HRFI females. This study was the first to verify that long-term divergent selection for RFI in Chinese broiler chickens is positive and beneficial.


Subject(s)
Chickens , Eating , Animals , Female , Male , Animal Feed/analysis , Cecum , Chickens/genetics , Phenotype
4.
Mol Biol Rep ; 50(1): 899-906, 2023 Jan.
Article in English | MEDLINE | ID: mdl-36309616

ABSTRACT

BACKGROUND: Breast cancer is the leading cause of death from cancer in women worldwide. STAMBP functions as a JAMM family deubiquitinating enzyme that modulates the stability of substrate proteins in cells by cleaving ubiquitin moieties. The expression of STAMBP and its clinical significance in breast cancer remain unclear. METHODS AND RESULTS: The level of the STAMBP protein in noncancerous and tumor tissues of breast cancer patients was examined by immunohistochemical staining. The expression of STAMBP mRNA in tissues based on healthy individual and breast cancer patient data in the TCGA database was evaluated. The association between the expression of STAMBP mRNA and clinical features and prognosis was evaluated using TCGA database. Cell growth was assessed by Cell Counting Kit-8 (CCK-8) assay, and cell migration and invasion were assessed by wound healing and Transwell assays. Activation of the ERK signaling was detected by Western blotting. The expression of STAMBP was markedly upregulated in the cytoplasm of tumor cells from breast cancer patients. The level of STAMBP was closely associated with the tumor subtype and size and the TNM stage of the breast cancer patients. Importantly, high expression of STAMBP predicted poor overall survival (OS) for breast cancer patients. Furthermore, knockdown of STAMBP expression reduced cell mobility and invasion of breast cancer cells. Notably, the phosphorylation of EGFR and ERK was markedly reduced in STAMBP-knockdown cells. CONCLUSION: STAMBP plays a critical role in the progression of breast cancer and may serve as a biomarker to monitor the progression of the disease.


Subject(s)
Breast Neoplasms , Humans , Female , Breast Neoplasms/metabolism , Cell Line, Tumor , Clinical Relevance , Signal Transduction/genetics , RNA, Messenger , Cell Movement/genetics , Cell Proliferation/genetics , Gene Expression Regulation, Neoplastic , Ubiquitin Thiolesterase/genetics , Ubiquitin Thiolesterase/metabolism , Endosomal Sorting Complexes Required for Transport/metabolism
5.
J Cancer ; 12(16): 4945-4957, 2021.
Article in English | MEDLINE | ID: mdl-34234864

ABSTRACT

Lung cancer is the second most common cancer in both men and women. The deubiquitinase PSMD7, as a core component of the 26S proteasome, is critical for the degradation of ubiquitinated proteins in the proteasome. Currently, PSMD7 expression and its roles in the progression of lung cancer remain largely unknown. In this study, we assessed PSMD7 expression and investigated the underlying molecular events by which PSMD7 regulates tumor progression in non-small cell lung cancer (NSCLC). The results showed that PSMD7 is more highly expressed in NSCLC tissues than in adjacent noncancerous tissues. PSMD7 expression was also closely associated with lymph node invasion and the laterality of the tumor in lung adenocarcinoma (LUAD). A high PSMD7 level predicted poor overall survival (OS) and disease-free survival (DFS) in LUAD patients, and PSMD7 knockdown significantly reduced cell proliferation and induced G0/G1-phase cell cycle arrest, cell senescence and apoptosis. PSMD7 knockdown inhibited expression of a set of proteins regulating cell cycle progression. Depletion of PSMD7 increased p53 levels and induced p21 and puma expression in a p53-dependent manner. Importantly, knockdown of PSMD7 markedly inhibited LUAD tumor growth in a xenograft mouse model. Taken together, these findings indicate that PSMD7 may serve as a valuable prognostic indicator and potential therapeutic target in LUAD.

6.
Neoplasia ; 23(6): 607-623, 2021 06.
Article in English | MEDLINE | ID: mdl-34102455

ABSTRACT

Tumor metastasis is a leading cause of death in lung adenocarcinoma (LUAD) patients, but the molecular events that regulate metastasis have not been completely elucidated. STAMBP is a deubiquitinating enzyme of the Jab1/MPN metalloenzyme family that regulates the stability of substrates in cells by specifically removing ubiquitin molecules. We found that STAMBP expression was increased in the cytoplasm of tumor cells from LUAD patients. The STAMBP level was closely associated with tumor size, lymph node invasion and neoplasm disease stage. A high STAMBP level predicted poor overall survival and disease-free survival in LUAD patients. STAMBP overexpression promoted cell migration and invasion, whereas STAMBP knockdown attenuated these processes in LUAD cells after epidermal growth factor treatment. Mechanistically, increased STAMBP expression promoted the stabilization of Epidermal growth factor receptor (EGFR), whereas STAMBP knockdown induced the degradation of EGFR. STAMBP may deubiquitinate EGFR by localizing in early endosomes and increase EGFR membrane localization in LUAD cells. The overexpression of STAMBP triggered the activation of MAPK signaling after epidermal growth factor treatment. In contrast, this activation was attenuated in STAMBP knockdown cells. Small molecule inhibitors of EGFR and MAPK signaling pathway may block STAMBP-induced cell mobility and invasion as well as ERK activation in cells. Importantly, STAMBP knockdown suppressed LUAD tumor growth and metastasis by regulating the EGFR-mediated ERK activation in a xenograft mouse model. Our findings identified STAMBP as a novel potential target for LUAD therapy.


Subject(s)
Adenocarcinoma of Lung/genetics , Adenocarcinoma of Lung/metabolism , Endosomal Sorting Complexes Required for Transport/genetics , Mitogen-Activated Protein Kinases/metabolism , Signal Transduction , Ubiquitin Thiolesterase/genetics , Adenocarcinoma of Lung/drug therapy , Adenocarcinoma of Lung/pathology , Adult , Aged , Animals , Cell Line, Tumor , Cell Movement/genetics , Disease Models, Animal , Endosomal Sorting Complexes Required for Transport/metabolism , Endosomes/metabolism , ErbB Receptors/metabolism , Female , Gene Expression , Gene Knockdown Techniques , Humans , Immunohistochemistry , Male , Mice , Middle Aged , Neoplasm Metastasis , Neoplasm Staging , Protein Kinase Inhibitors/pharmacology , Protein Transport , Signal Transduction/drug effects , Ubiquitin Thiolesterase/metabolism , Ubiquitination , Xenograft Model Antitumor Assays
7.
Am J Transl Res ; 12(9): 5433-5448, 2020.
Article in English | MEDLINE | ID: mdl-33042429

ABSTRACT

Breast cancer is the most common malignant tumor and the leading cause of cancer-related death in women. The ubiquitin-proteasome system regulates the stability of most proteins controlling various biological processes in human cells. PSMD7, as a core component of the 26S proteasome, is critical for the degradation of ubiquitinated proteins in the proteasome. Currently, PSMD7 expression and its roles in the progression of breast cancer remain largely unknown. In this study, we assessed the level of PSMD7 in breast cancer tissues and investigated the underlying molecular events by which PSMD7 could play a role in tumor progression. The results showed that the PSMD7 level was significantly upregulated in breast cancer tissues. PSMD7 expression was closely associated with tumor subtype, tumor size, lymph node invasion, and TNM stage. A high PSMD7 level predicted poor overall survival (OS) and disease-free survival (DFS) in breast cancer patients. Furthermore, univariate Cox regression analysis indicated that lymph node invasion, distant metastasis, and PSMD7 expression were associated with OS and DFS. Multivariate regression analysis indicated that PSMD7 was an independent predictor of OS (HR=1.310, 95% CI=1.038-1.652). Importantly, PSMD7 knockdown induced cell cycle arrest in the G0/G1 phase, leading to cell senescence and apoptosis. PSMD7 knockdown inhibited the expression of key cell cycle-related proteins and promoted the stability of p21 and p27 in breast cancer cells. PSMD7 may be a valuable prognostic indicator and potential therapeutic target for breast cancer.

8.
J Cancer ; 11(22): 6675-6685, 2020.
Article in English | MEDLINE | ID: mdl-33046988

ABSTRACT

Lung cancer is one of the most common malignant tumors in the world, with a high rate of malignancy and mortality. Seeking new biomarkers and potential drug targets is urgent for effective treatment of the disease. Deubiquitinase UCHL5/UCH37, as an important component of the 26S proteasome, plays critical roles in ubiquitinated substrate degradation. Although previous studies have shown that UCHL5 promotes tumorigenesis, its role in lung cancer remains largely unknown. In this study, we evaluated the expression and clinical significance of UCHL5 in non-small cell lung cancer (NSCLC). The results demonstrated that the UCHL5 expression level was significantly upregulated in NSCLC tissues compared with the adjacent noncancerous tissues. The level of UCHL5 was associated with tumor size, lymph node invasion, TNM stage and malignant tumor history in patients with lung adenocarcinoma (LUAD). Importantly, high UCHL5 expression predicted a poor overall survival (OS) and a poor disease-free survival (DFS) in patients with LUAD. Univariate regression analysis showed that tumor size, lymph node invasion, TNM stage and UCHL5 expression were associated with OS and DFS in patients with LUAD. The multivariate analysis indicated that the UCHL5 expression level was an independent prognostic factor for OS (HR=1.171, 95% CI=1.052-1.303) and DFS (HR=1.143, 95% CI=1.031-1.267) in these patients. UCHL5 knockdown in LUAD cells significantly inhibited cell proliferation and reduced the expression of key cell cycle proteins. These findings indicate that UCHL5 may serve as a potential prognostic marker and a new therapeutic target for patients with LUAD.

9.
Poult Sci ; 99(8): 4044-4051, 2020 Aug.
Article in English | MEDLINE | ID: mdl-32731992

ABSTRACT

Intestinal microbiota is a critical determinant of growth and risk of metabolic diseases. Our previous studies showed that the locus rs16775833 within the DMRT1 gene is significantly associated with variation in the population structure of the gut microbiota, which is involved in determining the BW of the chicken. To assess the accuracy of correlation of rs16775833 located in the DMRT1 gene on microbial population and BW in birds, 2 genotypes GG and TT in the rs16775833 were identified in Chinese Yellow broiler breeders. We found that BW in the TT genotype group was significantly higher than in the GG genotype group at 7 and 13 wk of age in 777 female chickens. A full-length 16S rRNA sequencing approach was used to further evaluate the fecal bacterial composition of female broilers in 11 TT genotype chickens with high weight (HW-TT) and 11 GG genotype chickens with low weight (LW-GG) at 91 D of age. Partial least squares discriminant analysis revealed that the microbiota of the HW-TT and LW-GG females were clearly separated into 2 clusters. Furthermore, we identified 13 significantly different (P < 0.05) microbes at the genus level and 17 significantly different (P < 0.05) species between the HW-TT and LW-GG groups. Our data show that rs16775833 can modulate the microbial community structure and is associated with the BW of birds. To our knowledge, this is the first time that DMRT1 has been identified as a specific host factor, which is not only involved in sex determination but also has an effect on microbial function that might regulate animal growth.


Subject(s)
Body Weight , Chickens , Gastrointestinal Microbiome , Transcription Factors , Animals , Body Weight/genetics , Chickens/genetics , Chickens/microbiology , Female , Gastrointestinal Microbiome/genetics , Genotype , RNA, Ribosomal, 16S/genetics , Transcription Factors/genetics
10.
Abdom Radiol (NY) ; 45(9): 2637-2646, 2020 09.
Article in English | MEDLINE | ID: mdl-32514628

ABSTRACT

PURPOSE: To determine if clinical characteristics of pregnant women are associated with the likelihood of ultrasound (US) visualization of the appendix in cases where there is a clinical suspicion of appendicitis. MATERIALS AND METHODS: A retrospective study of 471 pregnant patients with suspicion of appendicitis from 2009 to 2018 were studied. Patients underwent sonography of the appendix as their initial imaging study. The association of body mass index (BMI) and gestational age with sonographic visualization of the appendix was analyzed using logistic regression. Cut-off values were determined for BMI to predict visualization of the appendix. RESULTS: The rate of visualization of the appendix on US was 16% (95% CI 12% to 19%). When stratified by trimester of pregnancy, rebound pain on compression US examination in the 1st trimester and BMI in the 2nd and 3rd trimesters were identified as predictors of US visualization. Applying BMI cut-off values rounded to the nearest whole number, 36, 30, and 26 in the 1st, 2nd, and 3rd trimesters, non-visualization rates would be reduced by 16% (95% CI 10% to 25%), 35% (95% CI 29% to 42%), and 67% (95% CI 58% to 74%). Using BMI index cut-off values would reduce the number of primary US examinations by 35% (95% CI 30% to 39%) and increase the rate of visualization by 6% (95% CI 0.02% to 12%, P = 0.04). CONCLUSION: Using BMI cut-off values for determining the efficaciousness of US visualization of the appendix in pregnant women with suspicion of appendicitis could significantly reduce the non-visualization rate.


Subject(s)
Appendicitis , Appendix , Appendicitis/diagnostic imaging , Appendix/diagnostic imaging , Body Mass Index , Female , Humans , Pregnancy , Pregnant Women , Retrospective Studies , Ultrasonography
11.
ACS Appl Mater Interfaces ; 11(22): 20304-20315, 2019 Jun 05.
Article in English | MEDLINE | ID: mdl-31056910

ABSTRACT

Rheumatoid arthritis (RA) is a chronic, systemic, progressive autoimmune disease. The vascular permeability of inflamed joints in RA makes it a natural candidate for passive targeting, similar to the enhanced permeability and retention (EPR) effect in solid tumors. Thus, various therapeutic drugs have been encapsulated in nanocarriers to achieve longer in vivo circulation times and improve RA targeting. Although liposomes are the most widely used nanocarriers for RA treatment, the effects of physical and chemical characteristics of liposomes, such as particle sizes, surface charge, polyethylene glycol (PEG) chain length, and PEG concentration, on their passive RA targeting effect have not been fully elucidated. Here, we systematically investigated the effects of physical and chemical properties of liposomes on circulation time and conducted preliminary studies on their passive targeting mechanisms. A series of liposomes with different particle sizes (70, 100, 200, and 350 nm), surface charges (positive, negative, slight positive, and slight negative), PEG chain lengths (1, 2, and 5 kDa), and concentrations (5, 10, and 20% w/w of total lipid) were prepared by lipid film dispersion and extrusion. The pharmacokinetics of liposomes with different formulas were evaluated with a fluorescence microplate reader. A collagen-induced arthritis (CIA) mouse model was utilized to mimic RA pathological conditions and to evaluate the targeting and efficacy of liposomes with different properties using a near-infrared fluorescence imaging system. Uptake of fluorescent liposomes by various synovial cells was measured by flow cytometry. The results indicated that liposomes with 100 nm diameter, a slight negative charge, and 10% incorporation of 5 kDa PEG had better in vivo circulation time and inflamed joint targeting than did other liposomes. Dexamethasone (Dex) was encapsulated into optimized liposomes as an active ingredient for RA treatment. Pharmacodynamic studies demonstrated that Dex liposomes could significantly improve the antiarthritic efficacy of Dex in a CIA mouse model of RA. This study also found that the retention mechanism of RA was mainly increased because of the uptake of liposomes by fibroblasts and macrophages in inflamed joints. This study provides a persuasive explanation for passive RA targeting by liposomes and advances our ability to treat RA with nanomedicine.


Subject(s)
Arthritis, Rheumatoid/drug therapy , Liposomes/chemistry , Polyethylene Glycols/chemistry , Animals , Dexamethasone/chemistry , Dexamethasone/therapeutic use , Disease Models, Animal , Flow Cytometry , Male , Mice , Nanomedicine/methods
12.
Cancer Lett ; 443: 13-24, 2019 02 28.
Article in English | MEDLINE | ID: mdl-30503558

ABSTRACT

Advanced stage nasopharyngeal carcinoma (NPC) has a poor prognosis. Triptonide ("TN") is a small molecule monomer extract from the ancient Chinese herb Tripterygium wilfordii Hook. We show that TN, at nanomolar concentrations, potently inhibited survival and proliferation of multiple established and primary human NPC cells. TN induced NPC cell cycle arrest and apoptosis activation. NPC cell migration and invasion were also inhibited by TN. Importantly, TN was non-cytotoxic to nasopharyngeal epithelial cells. TN treatment in NPC cells disrupted LncRNA THOR ("Lnc-THOR")-IGF2BP1 association, causing depletion of Lnc-THOR and downregulation of IGF2BP1 mRNA targets (Myc, IGF2 and Gli1). Lnc-THOR or IGF2BP1 knockout by CRISPR/Cas9 gene-editing methods mimicked and abolished TN's actions in NPC cells. Conversely, ectopic Lnc-THOR overexpression inhibited TN-induced cytotoxicity in NPC cells. Significantly, Lnc-THOR, IGF2BP1 and its mRNA targets are elevated in human NPC tissues and cells, but almost undetectable in nasopharyngeal epithelial tissues and cells. In vivo, intraperitoneal TN administration significantly inhibited subcutaneous NPC xenograft growth in mice. Similarly, Lnc-THOR-knockout HONE-1 xenografts grew significantly slower than control tumors. Thus, TN inhibits human NPC cell growth in vitro and in vivo via disrupting Lnc-THOR-IGF2BP1 signaling.


Subject(s)
Antineoplastic Agents, Phytogenic/administration & dosage , Nasopharyngeal Carcinoma/drug therapy , Nasopharyngeal Neoplasms/drug therapy , Signal Transduction/drug effects , Triterpenes/administration & dosage , Animals , Antineoplastic Agents, Phytogenic/pharmacology , Cell Movement/drug effects , Cell Proliferation/drug effects , Gene Expression Regulation, Neoplastic/drug effects , Humans , Injections, Intraperitoneal , Male , Mice , Middle Aged , Nasopharyngeal Carcinoma/genetics , Nasopharyngeal Neoplasms/genetics , RNA, Long Noncoding/genetics , RNA-Binding Proteins/genetics , Triterpenes/pharmacology , Tumor Cells, Cultured , Xenograft Model Antitumor Assays
13.
Drug Deliv ; 24(1): 752-764, 2017 Nov.
Article in English | MEDLINE | ID: mdl-28468542

ABSTRACT

To conquer the drug resistance of tumors and the poor solubility of paclitaxel (PTX), two PTX-cell-penetrating peptide conjugates (PTX-CPPs), PTX-TAT and PTX-LMWP, were synthesized and evaluated for the first time. Compared with free PTX, PTX-CPPs displayed significantly enhanced cellular uptake, elevated cell toxicity, increased cell apoptosis, and decreased mitochondrial membrane potential (Δψm) in both A549 and A549T cells. PTX-LMWP exhibited a stronger inhibitory effect than PTX-TAT in A549T cells. Analysis of cell-cycle distribution showed that PTX-LMWP influenced mitosis in drug-resistant A549T tumor cells via a different mechanism than PTX. PTX-CPPs were more efficient in inhibiting tumor growth in tumor-bearing mice than free PTX, which suggested their better in vivo antitumor efficacy. Hence, this study demonstrates that PTX-CPPs, particularly PTX-LMWP, have outstanding potential for inhibiting the growth of tumors and are a promising approach for treating lung cancer, especially drug-resistant lung cancer.


Subject(s)
Drug Resistance, Neoplasm , Lung Neoplasms , A549 Cells , Animals , Antineoplastic Agents, Phytogenic , Apoptosis , Cell-Penetrating Peptides , Humans , Mice , Paclitaxel
14.
ACS Appl Mater Interfaces ; 9(7): 5864-5873, 2017 Feb 22.
Article in English | MEDLINE | ID: mdl-28128553

ABSTRACT

Chemotherapy outcomes for the treatment of glioma remain unsatisfied due to the inefficient drug transport across BBB/BBTB and poor drug accumulation in the tumor site. Nanocarriers functionalized with different targeting ligands are considered as one of the most promising alternatives. However, few studies were reported to compare the targeting efficiency of the ligands and develop nanoparticles to realize BBB/BBTB crossing and brain tumor targeting simultaneously. In this study, six peptide-based ligands (Angiopep-2, T7, Peptide-22, c(RGDfK), D-SP5 and Pep-1), widely used for brain delivery, were selected to decorate liposomes, respectively, so as to compare their targeting ability to BBB or BBTB. Based on the in vitro cellular uptake results on BCECs and HUVECs, Peptide-22 and c(RGDfK) were picked to construct a BBB/BBTB dual-crossing, glioma-targeting liposomal drug delivery system c(RGDfK)/Pep-22-DOX-LP. In vitro cellular uptake demonstrated that the synergetic effect of c(RGDfK) and Peptide-22 could significantly increase the internalization of liposomes on U87 cells. In vivo imaging further verified that c(RGDfK)/Pep-22-LP exhibited higher brain tumor distribution than single ligand modified liposomes. The median survival time of glioma-bearing mice treated with c(RGDfK)/Pep-22-DOX-LP (39.5 days) was significantly prolonged than those treated with free doxorubicin or other controls. In conclusion, the c(RGDfK) and Peptide-22 dual-modified liposome was constructed based on the targeting ability screening of various ligands. The system could effectively overcome BBB/BBTB barriers, target to tumor cells and inhibit the growth of glioma, which proved its potential for improving the efficacy of chemotherapeutics for glioma therapy.


Subject(s)
Glioma , Animals , Blood-Brain Barrier , Brain Neoplasms , Cell Line, Tumor , Drug Delivery Systems , Liposomes , Mice , Mice, Inbred BALB C , Peptides , Peptides, Cyclic
15.
Zhongguo Zhen Jiu ; 35(8): 819-22, 2015 Aug.
Article in Chinese | MEDLINE | ID: mdl-26571901

ABSTRACT

OBJECTIVE: To compare the differences in the characteristic medicinal cupping therapy between the traditional cupping device and the innovated cupping device. METHODS: Fifty patients of neck and low back pain were selected. The self-comparison was adopted. The cupping therapy was applied to the acupoints located on the left or right side with the traditional cupping device and the innovated cupping device. The cupping sites were centered at bilateral Quyuan (SI 13) and Dachangshu (BL 25). The cups were retained for 10 min. The traditional cupping device was the glass with smooth border, 100mL. The innovated cupping device was the vacuum-sucking cup. The operative time, medicinal leakage, comfort and cupping marks were observed for the two different cupping devices. RESULTS: The operative time with the innovated medicinal cupping device was shorter obviously compared with the traditional one at Quyuan (SI 13) and Dachangshu (BL 25, both P<0. 05). The comfort with the innovated medicinal cupping device was remarkably improved as compared with the traditional one at the two acupoints (both P<0. 05). The medicinal leakage was similar between the two different devices during the cupping operation (both P>0. 05). The cupping marks with the innovated medicinal cupping device were much deeper than those with the traditional one after cupping therapy. CONCLUSION: The innovated cupping device is more convenent and comfortable in operation during the characteristic medicinal cupping therapy.


Subject(s)
Low Back Pain/therapy , Medicine, Chinese Traditional/instrumentation , Neck Pain/therapy , Acupuncture Points , Adult , Aged , Aged, 80 and over , Female , Humans , Male , Medicine, Chinese Traditional/methods , Meridians , Middle Aged , Young Adult
16.
J Pharm Biomed Anal ; 112: 98-105, 2015 Aug 10.
Article in English | MEDLINE | ID: mdl-25974727

ABSTRACT

Compound Danshen Dripping Pill (CDDP) has been used for the treatment of coronary heart disease for decades. We aimed to increase the understanding of the mechanisms by evaluating the urinary metabolomics of CDDP using Gas Chromatography-Mass Spectrometer (GC-MS) in a myocardial ischaemia (MI) rat model. One hundred Sprague-Dawley rats were divided into Con (normal saline and no surgery), Con+ (107 mg/kg d CDDP solution and no surgery), Sham (normal saline and surgery without aorta ligation), Mod (normal saline and surgery with aorta ligation), and Mod+ (107 mg/kg d CDDP solution and surgery with aorta ligation) groups. Urine samples on days 0, 3, 14, and 28 were tested using GC-MS and analyzed with PCA and partial least squares-discriminant analysis models. In the Mod group, creatine kinase and malondialdehyde levels were higher, and superoxide-dismutase levels were lower; the same variables normalized in the Mod+ group. CDDP resulted in improvement in the Mod+ group, as indicated by the reduced necrosis in the myocardial tissue. A total of 36 metabolites were identified in the urine samples, and 8 metabolites (malate, succinate, creatinine, methionine, cysteine, serine, phenylalanine, and tyrosine) were increased remarkably and recovered to normal levels after treatment with CDDP. Differentially expressed metabolites implied that energy, amino acid, fatty acid, and polyol metabolism might be disrupted by MI and reversed by CDDP. Urinary metabolomics provide a dynamic monitoring approach that highlights interference by MI and the therapeutic effects of CDDP on MI in rats throughout the recovery process.


Subject(s)
Drugs, Chinese Herbal/chemistry , Drugs, Chinese Herbal/metabolism , Myocardial Ischemia/metabolism , Myocardial Ischemia/urine , Myocardium/metabolism , Animals , Creatine Kinase/metabolism , Gas Chromatography-Mass Spectrometry/methods , Male , Malondialdehyde/metabolism , Metabolomics/methods , Necrosis/metabolism , Necrosis/urine , Rats , Rats, Sprague-Dawley , Salvia miltiorrhiza , Superoxide Dismutase/metabolism
17.
Article in English | MEDLINE | ID: mdl-23737844

ABSTRACT

Coronary heart disease (CHD) is one of the highest mortality diseases in the world. Traditional Chinese medicine compound Danshen dripping pills (CDDPs) have currently made a great achievement in treating CHD. However, the therapeutic mechanism of CDDP is often poorly interpreted. In this study, a GC-MS-based metabonomic study was conducted to assess the holistic efficacy of CDDP for myocardial infarction in male Sprague-Dawley rats, which were divided into the control group, the sham group, the model group, the control + CDDP group, and the model + CDDP, with CDDP at a dose of 107 mg/kg·d (equal to 1.8 mL/kg·d). The metabonomic findings demonstrated great differences of metabolic pattern among sham, model, and the model + CDDP in the orthogonal partial least squares discriminant analysis (OPLS-DA) models, which coordinated well with the assessment of plasma biochemistry and histopathological assay. Differentially expressed metabolites suggested that energy metabolism, glycolysis, and lipid metabolism might be disrupted by myocardial infarction. Both the potential metabolic biomarkers and the biochemical histopathological indices were regulated effectively by CDDP.

18.
Zhongguo Zhong Yao Za Zhi ; 36(16): 2294-6, 2011 Aug.
Article in Chinese | MEDLINE | ID: mdl-22097348

ABSTRACT

OBJECTIVE: To observe the impact of Sanjin tablet on the T lymphocyte subsets of the peripheral blood of female patients with recurrent urinary tract infection, to reveal the immune pharmacological mechanism of its prevention and treatment of the disease. METHOD: A randomized, controlled and open trial was adopted. The 68 patients were divided into treatment group (30 cases) and control group (28 cases). Two groups were both treated with conventional sensitive antibiotics, the treatment group took Sanjin tablet in addition. After bacteria in the urine were negative, the treatment group took maintenance therapy with Sanjin tablet for 3 months, the control group took appropriate low-dose antibiotics maintenance treatment for 3 months. The peripheral blood T lymphocyte levels before and after treatment, time from the initial treatment to the bacterial culture of urine was negative of the two groups, and the recurrence rate of urinary tract infection in 3 months after discontinuation of the two groups were observed. RESULT: After treatment, the CD3+, CD4+ T cells and CD4+/CD8+ in peripheral blood of the treatment group were enhanced compared with untreated and the control group (P < 0.05). Time from the initial treatment to the bacterial was negative and the recurrence rate of the treatment group were significantly better than the control group (P < 0.01). CONCLUSION: Effective treatment with Sanjin tablet to the recurrent urinary tract infection of female patients will probablely through the mechanism of improving the cell-mediated immunity levels to achieve the effect of shortening the course of treatment and to reducing the recurrence rate.


Subject(s)
Drugs, Chinese Herbal/therapeutic use , T-Lymphocyte Subsets/drug effects , Urinary Tract Infections/drug therapy , Adult , Aged , Humans , Male , Middle Aged , Recurrence , Tablets , Urinary Tract Infections/immunology
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