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1.
APL Bioeng ; 8(2): 026107, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38694891

ABSTRACT

Establishing quantitative parameters for differentiating between healthy and diseased cartilage tissues by examining collagen fibril degradation patterns facilitates the understanding of tissue characteristics during disease progression. These findings could also complement existing clinical methods used to diagnose cartilage-related diseases. In this study, cartilage samples from normal, osteoarthritis (OA), and rheumatoid arthritis (RA) tissues were prepared and analyzed using polarization-resolved second harmonic generation (P-SHG) imaging and quantitative image texture analysis. The enhanced molecular contrast obtained from this approach is expected to aid in distinguishing between healthy and diseased cartilage tissues. P-SHG image analysis revealed distinct parameters in the cartilage samples, reflecting variations in collagen fibril arrangement and organization across different pathological states. Normal tissues exhibited distinct χ33/χ31 values compared with those of OA and RA, indicating collagen type transition and cartilage erosion with chondrocyte swelling, respectively. Compared with those of normal tissues, OA samples demonstrated a higher degree of linear polarization, suggesting increased tissue birefringence due to the deposition of type-I collagen in the extracellular matrix. The distribution of the planar orientation of collagen fibrils revealed a more directional orientation in the OA samples, associated with increased type-I collagen, while the RA samples exhibited a heterogeneous molecular orientation. This study revealed that the imaging technique, the quantitative analysis of the images, and the derived parameters presented in this study could be used as a reference for disease diagnostics, providing a clear understanding of collagen fibril degradation in cartilage.

2.
J Multidiscip Healthc ; 16: 4149-4159, 2023.
Article in English | MEDLINE | ID: mdl-38143798

ABSTRACT

Purpose: The present study aims to examine the disparate effects of health behavior models, namely exercise self-efficacy (ESE), health belief model (HBM), and planned behavior theory (PBT), applied to clarify the degree of regular exercise among workers in Taiwan. Methods: A cross-sectional research design was adopted. A questionnaire was distributed to obtain information pertaining to regular exercise level, demographic characteristics, and the scores of ESE, HBM, and PBT. In total, 400 full-time workers voluntarily participated in this study. Results: The results showed that only 20.5% of the participants exercised regularly, 37.3% exercised irregularly, and 42.3% did not exercise currently. "Perceived benefits" and "perceived barriers" pertaining to HBM; "attitude" and "perceived behavioral control" pertaining to PBT; and ESE were associated with regular exercise level in the multiple linear regression analyses of each health behavior model. When all three models were considered simultaneously, ESE provided the greatest explanation of the variances for regular exercise levels. PBT total made a smaller contribution in the prediction of regular exercise level, while the effect of HBM did not show statistical significance. In order to explore the practicality of moving beyond theoretical models and focusing on the components across health behavior models to enhance workers' exercise behavior, the components showing statistical significance in separate analysis were put into the multiple linear regression simultaneously. The results showed that ESE, perceived barriers of health behavior, attitude, and perceived behavioral control were significantly associated with regular exercise level. Conclusion: A low percentage of workers exercising regularly should be a notable issue for workplace health promotion. Neither utilizing cues to exercise nor advertising health threats of physical inactivity is sufficient to enable workers to exercise regularly. Enhancing workers' ESE and behavior control and removing the exercise barriers would constitute efficient strategies for maintaining the exercise habit of workers.

3.
Int J Mol Sci ; 24(18)2023 Sep 05.
Article in English | MEDLINE | ID: mdl-37761992

ABSTRACT

Due to the overconsumption of antimicrobials, antibiotic-resistant bacteria have become a critical health issue worldwide, especially methicillin-resistant S. aureus (MRSA) and vancomycin-resistant E. faecalis (VRE). Recently, many efforts have been made to load metals into bioactive glasses to enhance the multifunctionality of materials, such as antibacterial and osteoinductive functions. Zinc has been documented to stimulate the gene expression of various regulatory factors in bone cells. Meanwhile, previous studies have reported that silver and zinc could be a promising antibacterial combination with synergistic antimicrobial effects. Here, we sought to develop a biomaterial coreleasing zinc and silver, designated 80S-ZnAg, and to evaluate its antibacterial activity and biocompatibility. The textural analyses demonstrated different coreleasing patterns of zinc and silver for the materials. The chemical characterization revealed that the zinc in 80S-ZnAg could be the network modifier when its molar ratio was high, releasing more zinc; zinc could also be the network former when its molar ratio was low, showing an extremely low rate of release. However, the ICP results for 80S-Zn3Ag2 demonstrated up to 7.5 ppm of zinc and 67.6 ppm of silver. Among all the 80S-ZnAg materials, 80S-Zn3Ag2 demonstrated more marked antibacterial activity against MRSA and VRE than the others, with inhibition zones of 11.5 and 13.4 mm, respectively. The cytotoxicity assay exhibited nearly 90% cell viability at 20 mg/mL of 80-Zn3Ag2. Further clinical study is needed to develop an innovative biomaterial to address the issue of antibiotic resistance.


Subject(s)
Methicillin-Resistant Staphylococcus aureus , Silver/pharmacology , Silver/chemistry , Zinc/pharmacology , Anti-Bacterial Agents/pharmacology , Anti-Bacterial Agents/chemistry , Biocompatible Materials/pharmacology , Microbial Sensitivity Tests
4.
Pharmaceuticals (Basel) ; 16(9)2023 Aug 22.
Article in English | MEDLINE | ID: mdl-37764996

ABSTRACT

BACKGROUND: The local tumor control rate of colon cancer by radiotherapy is unsatisfactory due to recurrence and radioresistance. Ginsenoside Rh2 (Rh2), a panoxadiol saponin, possesses various antitumor effects. METHODS: CT26/luc murine colon carcinoma cells and a CT26/luc tumor-bearing animal model were used to investigate the therapeutic efficacy of Rh2 combined with ionizing radiation and the underlying mechanisms. RESULTS: Rh2 caused cell cycle arrest at the G1 phase in CT26/luc cells; however, when combined with ionizing radiation, the cells were arrested at the G2/M phase. Rh2 was found to suppress the activity of NF-κB induced by radiation by inhibiting the MAPK pathway, consequently affecting the expression of effector proteins. In an in vivo study, the combination treatment significantly increased tumor growth delay time and overall survival. Furthermore, the combination treatment significantly reduced NF-κB and NF-κB-related effector proteins, along with PD-1 receptor expression. Additionally, Rh2 administration led to increased levels of interleukin-12, -18, and interferon-γ in the mice's sera. Importantly, biochemical analysis revealed no toxicities associated with Rh2 alone or combined with radiation. CONCLUSIONS: The combination of Rh2 with radiation may have potential as an alternative to improve the therapeutic efficacy of colorectal cancer.

5.
Sensors (Basel) ; 23(13)2023 Jun 26.
Article in English | MEDLINE | ID: mdl-37447763

ABSTRACT

With the rapid advancement of information and communication technology (ICT), big data, and artificial intelligence (AI), intelligent healthcare systems have emerged, including the integration of healthcare systems with capital, the introduction of healthcare systems into long-term care institutions, and the integration of measurement data for care or exposure. These systems provide comprehensive communication and home exposure reports and enable the involvement of rehabilitation specialists and other experts. Silver technology enables the realization of health management in long-term care services, workplace care, and health applications, facilitating disease prevention and control, improving disease management, reducing home isolation, alleviating family burden in terms of nursing, and promoting health and disease control. Research and development efforts in forward-looking cross-domain precision health technology, system construction, testing, and integration are carried out. This integrated project consists of two main components. The Integrated Intelligent Long-Term Care Service Management System focuses on building a personalized care service system for the elderly, encompassing health, nutrition, diet, and health education aspects. The Wearable Internet of Things Care System primarily supports the development of portable physiological signal detection devices and electronic fences.


Subject(s)
Artificial Intelligence , Wearable Electronic Devices , Humans , Aged , Long-Term Care , Delivery of Health Care , Technology
6.
Microsc Microanal ; 29(4): 1450-1459, 2023 07 25.
Article in English | MEDLINE | ID: mdl-37488816

ABSTRACT

Starch is a semi-crystalline macromolecule with the presence of amorphous and crystalline components. The amorphous amylose and crystalline amylopectin regions in starch granules are susceptible to certain physical modifications, such as gamma irradiation. Polarization-resolved second harmonic generation (P-SHG) microscopy in conjunction with SHG-circular dichroism (CD) was used to assess the three-dimensional molecular order and inherent chirality of starch granules and their reaction to different dosages of gamma irradiation. For the first time, the relationship between starch achirality (χ21/χ16 and χ22/χ16) and chirality (χ14/χ16) determining susceptibility tensor ratios has been elucidated. The results showed that changes in the structure and orientation of long-chain amylopectin were supported by the decrease in the SHG anisotropy factor and the χ22/χ16 ratio. Furthermore, SHG-CD illustrated the molecular tilt angle by revealing the arrangement of amylopectin molecules pointing either upward or downward owing to molecular polarity.


Subject(s)
Amylopectin , Second Harmonic Generation Microscopy , Starch
7.
Pharmaceuticals (Basel) ; 14(11)2021 Nov 04.
Article in English | MEDLINE | ID: mdl-34832906

ABSTRACT

The aim of this study was to evaluate the remineralization and antibacterial effect of silver-containing mesoporous bioactive glass (MBG-Ag) sealing combined with Er:YAG laser irradiation on human demineralized dentin specimens in a Streptococcus mutans cultivated environment. A total of 48 human dentin specimens were randomly divided into four groups. The characteristics of MBG-Ag and the occlusion efficiency of the dentinal tubules were analyzed using X-ray diffraction patterns, Fourier-transform infrared spectroscopy, scanning electron microscope images and energy dispersive X-ray spectroscopy. Moreover, the antibacterial activity against Streptococcus mutans was evaluated by colony formation assay. The results showed that the dentin specimens with Er:YAG laser irradiation can form a melted occlusion with a size of 3-4 µm. MBG-Ag promoted the deposition of numerous crystal particles on the dentinal surface, reaching the deepest penetration depth of 70 µm. The results suggested that both MBG-Ag and laser have the ability to enhance the remineralization and precipitation of hydroxyapatite crystals. While the results showed that MBG-Ag sealing combined with the thermomechanical subablation mode of Er:YAG laser irradiation-induced dense crystalline deposition, reaching a penetration depth of more than 300 µm, silver nanoparticles without good absorption of the Er:YAG laser resulted in a heterogeneous radiated surface. Er:YAG laser irradiation with a low energy and pulse rate cannot completely inhibit the growth of S. mutans, but MBG-Ag sealing reached the bactericidal concentration. It was concluded that the simultaneous application of MBG-Ag sealing and Er:YAG laser treatment can prevent the drawbacks of their independent uses, resulting in a superior form of treatment for dentin hypersensitivity.

8.
Materials (Basel) ; 14(18)2021 Sep 15.
Article in English | MEDLINE | ID: mdl-34576538

ABSTRACT

Sericin, a textile waste, can be used for antioxidant and skin-whitening purposes. The hydrothermal method of extracting sericin is more eco-friendly than are chemical and enzymatic methods. In this study, silk cocoons were cut into pieces and then subjected to hydrothermal extraction at three temperatures (160, 200, and 220 °C) to obtain sericin extracts (Sericin160, Sericin200, and Sericin220, respectively). Antioxidant activity and tyrosinase inhibition were measured to determine the extracts' effectiveness. Sericin220 was the strongest antioxidant, with total phenol content, total flavonoid content, and ferric reducing power of 62.19 ± 0.04 mg gallic acid equivalents/g dry weight, 0.07 ± 0.01 mg quercetin equivalent/g dry weight, and 181.49 ± 0.024 mg vitamin C equivalent/g dry weight, respectively. The half-maximal inhibitory concentrations for DPPH and ABTS free-radical scavenging ability were 6.41 ± 0.05 and 0.79 ± 0.37 mg/mL, respectively. Sericin220 also exhibited the highest tyrosinase inhibition activity (70.82 ± 4.1 mg vitamin C equivalent/g), indicating its whitening potential.

9.
Materials (Basel) ; 14(16)2021 Aug 19.
Article in English | MEDLINE | ID: mdl-34443200

ABSTRACT

Chenopodium formosanum (CF), rich in nutrients and antioxidants, is a native plant in Taiwan. During the harvest, the seeds are collected, while the roots, stems, and leaves remain on the field as agricultural waste. In this study, di(phenyl)-(2,4,6-trinitrophenyl)iminoazanium (DPPH) radical scavenging ability and 2,2'-azino-bis(3-ethylbenzthiazoline-6-sulfonic acid) (ABTS) radical scavenging ability experiments of seeds, leaves, stems, and roots were designed using the Taguchi method (TM) under three conditions: Ethanol concentration (0-100%), temperature (25-65 °C), and extraction time (30-150 min). The result demonstrates that seeds and leaves have higher radical scavenging ability than stems and roots. Many studies focused on CF seeds. Therefore, this study selected CF leaves and optimized DPPH, ABTS, total phenol content (TPC), total flavonoid content (TFC), and reducing power (RP) through TM, showing that the predicted value of the leaf is close to the actual value. The optimized results of CF leaves were DPPH 85.22%, ABTS 46.51%, TPC 116.54 µg GAE/mL, TFC 143.46 µg QE/mL, and RP 23.29 µg VCE (vitamin C equivalent)/mL. The DPPH and ABTS of CF leaves were second only to the results of CF seeds. It can be seen that CF leaves have the potential as a source of antioxidants and help in waste reduction.

10.
Polymers (Basel) ; 13(9)2021 May 10.
Article in English | MEDLINE | ID: mdl-34068784

ABSTRACT

Acinetobacter baumannii (A. baumannii) is a common and challenging pathogen of nosocomial infections, due to its ability to survive on inanimate objects, desiccation tolerance, and resistance to disinfectants. In this study, we investigated an antibacterial strategy to combat A. baumannii via the combination of antibiotics and silver protein. This strategy used a functional platform consisting of silver nanoparticles (AgNPs) resurrected from silver-based calcium thiophosphate (SSCP) through casein and arginine. Then, the silver protein was combined with tigecycline, the first drug in glycylcycline antibiotic, to synergistically inhibit the viability of A. baumannii. The synergistic antibacterial activity was confirmed by the 96-well checkerboard method to determine their minimum inhibitory concentrations (MIC) and calculated for the combination index (CI). The MIC of the combination of silver protein and tigecycline (0.31 mg/mL, 0.16 µg/mL) was significantly lower than that of the individual MIC, and the CI was 0.59, which indicates a synergistic effect. Consequently, we integrated the detailed synergistic antibacterial properties when silver protein was combined with tigecycline. The result could make for a promising approach for the treatment of A. baumannii.

11.
Biosci Rep ; 41(5)2021 05 28.
Article in English | MEDLINE | ID: mdl-33974005

ABSTRACT

Androgen deprivation therapy (ADT) is one of the typical treatments used for patients with prostate cancer (PCa). ADT, however, may fail when PCa develops castration-resistance. Fatty acid synthase (FASN), a critical enzyme involved in fatty acid synthesis, is found to be up-regulated in PCa. Since enzalutamide and ADT are frequently used for the treatment of PCa, the present study aimed to unravel the underlying mechanism of combination of orlistat, an FASN inhibitor, and enzalutamide using PC3 cell line; and orlistat and castration in PC3 tumor-bearing animal model. Cytotoxicity was determined by AlamarBlue assay. Drug effects on the cell cycle and protein expressions were assayed by the flow cytometry and Western blot. Electromobility shift assay was used to evaluate the NF-κB activity. The tumor growth delay, expressions of the signaling-related proteins, and histopathology post treatments of orlistat and castration were evaluated in PC3 tumor-bearing mouse model. The results showed that orlistat arrested the PC3 cells at the G1 phase of the cell cycle and enhanced the cytotoxic effects of enzalutamide synergistically. Pretreatment with orlistat combined with castration inhibited the tumor growth significantly compared with those of castration and orlistat treatments alone in PC3 tumor-bearing mice. Combination treatment reduced both FASN and NF-κB activities and their downstream effector proteins. The present study demonstrated the synergistic effects of orlistat combined with enzalutamide in vitro and castration in vivo on human PCa.


Subject(s)
Antineoplastic Agents/therapeutic use , Benzamides/therapeutic use , Enzyme Inhibitors/therapeutic use , Fatty Acid Synthase, Type I/antagonists & inhibitors , Nitriles/therapeutic use , Orlistat/therapeutic use , Phenylthiohydantoin/therapeutic use , Prostatic Neoplasms/drug therapy , Animals , Antineoplastic Agents/pharmacology , Benzamides/pharmacology , Cell Cycle/drug effects , Enzyme Inhibitors/pharmacology , Fatty Acid Synthase, Type I/metabolism , Humans , Male , Mice , Mice, Nude , NF-kappa B/metabolism , Nitriles/pharmacology , Orchiectomy/methods , Orlistat/toxicity , PC-3 Cells , Phenylthiohydantoin/pharmacology , Prostatic Neoplasms/surgery
12.
Nanomaterials (Basel) ; 10(7)2020 Jun 28.
Article in English | MEDLINE | ID: mdl-32605329

ABSTRACT

Staphylococcus aureus, which is commonly found in hospitals, has become a major problem in infection control. In this study, Ag/80S bioactive ceramics used for enhanced antibacterial applications have been developed. An in vitro bioactivity test of the Ag/80S bioactive ceramic powders was performed in a phosphate-buffered saline (PBS). To explore the antibacterial activity of the Ag/80S bioactive ceramic powders, the Kirby-Bauer susceptibility test, the kinetics of microbial growth analysis and the colony-forming capacity assay were used to determine their minimum inhibitory concentration (MIC) against methicillin-resistant Staphylococcus aureus (MRSA). The results confirmed that the Ag/80S bioactive ceramic powders have antibacterial activity against MRSA (ATCC 33592) and MRSA (ATCC 49476).

13.
Int J Mol Sci ; 21(12)2020 Jun 19.
Article in English | MEDLINE | ID: mdl-32575632

ABSTRACT

Glioblastoma, the most common and aggressive brain tumor with low survival rate, is difficult to be cured by neurosurgery or radiotherapy. Mounting evidence has reported the anti-inflammatory and anticancer effects of curcumin on several types of cancer in preclinical studies and clinical trials. To our knowledge, there is no platform or system that could be used to effectively and real-timely evaluate the therapeutic efficacy of curcumin for glioblastoma multiforme (GBM). In this study, we constructed a lentivirus vector with triple-reporter genes (Fluc/GFP/tk) and transduced into rat F98 glioblastoma cells to establish an orthotopic F98/FGT glioma-bearing rat model. In the model, the therapeutic efficacies for curcumin alone, radiation alone, and their combination were evaluated via noninvasive bioluminescent imaging and overall survival measurements. At the cell level, curcumin is capable of causing a G2/M cell cycle arrest and sensitizing the F98 cells to radiation. In animal model, curcumin synergistically enhances the effects of radiotherapy on suppressing the growth of both transplanted glioma cells and in situ brain tumors, and extending the overall survival periods longer than those of curcumin alone and radiation alone treatments. In conclusion, we have demonstrated that curcumin may serve as a novel radiosensitizer to combine with radiotherapy using the triple-reporter F98/FGT animal model for effective and simultaneous evaluation of therapeutic efficacy.


Subject(s)
Brain Neoplasms/therapy , Curcumin/administration & dosage , Glioblastoma/therapy , Lentivirus/genetics , Radiation-Sensitizing Agents/administration & dosage , Animals , Brain Neoplasms/diagnostic imaging , Brain Neoplasms/genetics , Cell Cycle/drug effects , Cell Cycle/radiation effects , Cell Line, Tumor , Cell Survival/drug effects , Cell Survival/radiation effects , Chemoradiotherapy , Curcumin/pharmacology , Glioblastoma/diagnostic imaging , Glioblastoma/genetics , Green Fluorescent Proteins/genetics , Green Fluorescent Proteins/metabolism , Luciferases/genetics , Luciferases/metabolism , Magnetic Resonance Imaging , Radiation-Sensitizing Agents/pharmacology , Rats , Rats, Transgenic , Thymidine Kinase/genetics , Thymidine Kinase/metabolism , Treatment Outcome , Xenograft Model Antitumor Assays
14.
Medicine (Baltimore) ; 99(18): e20072, 2020 May.
Article in English | MEDLINE | ID: mdl-32358388

ABSTRACT

Vertebral compression fractures (VCFs) are common in elderly and are treated with immobilization. Moreover, immobilization and old age may increase venous thromboembolism (VTE) risk. However, the incidence of VCFs-related VTE is unknown in elderly. The purposes of this study were to determine the incidence of VTE among VCF patients, to explore whether percutaneous vertebroplasty (PV) intervention may reduce VTE risk in VCFs patients.We conducted a population-based case-control study by using the National Health Insurance Research Database. We identified 1407 patients aged ≥65 with VCF who received PV and 1407 VCFs patients who did not receive PV after developing a 1:1 propensity score-matched study cohort and were followed up for 5 years. Using PV intervention as the exposure factor, a cause-specific Cox's proportional hazards model was used to examine the association between PV and VTE.After propensity score matching, the mean age of the study participants was 78 years and ∼23% of the analyzed participants were men, incidence of VTE in the PV and control cohorts was 5.77 and 4.19 per 1000 person-years, respectively. Both groups were nonsignificant difference after examination with different adjustment models. Patients with VCF and a history of heart failure, coronary artery disease, receiving antihypertension medication were at a significantly increased VTE risk.Elderly patients with VCF who received PV had a neutral impact on risk of VTE. VCF patients with heart failure, coronary artery disease, and receiving antihypertension medication were prone to developing VTE should be monitored cautiously.


Subject(s)
Fractures, Compression/epidemiology , Fractures, Compression/surgery , Spinal Fractures/epidemiology , Spinal Fractures/surgery , Venous Thromboembolism/epidemiology , Aged , Aged, 80 and over , Cardiovascular Diseases/epidemiology , Case-Control Studies , Comorbidity , Female , Humans , Male , Minimally Invasive Surgical Procedures , Propensity Score , Risk Factors , Socioeconomic Factors , Taiwan/epidemiology , Vertebroplasty/methods
15.
Article in English | MEDLINE | ID: mdl-32397534

ABSTRACT

This study aimed to investigate level of work ability and quality of life (QOL) as well as the relationship between them among patients suffering from work-related musculoskeletal disorders (WMSDs) in Taiwan. A cross-sectional study design with continuous sampling and a questionnaire were used to obtain the research data. Controlling for personal characteristics, pain, psychological distress, and social support, multiple linear regressions were adopted to explore the relationship between work ability and overall QOL. Further analyses were also made to clarify the relationships between work ability and each domain of QOL. In total, 165 patients with WMSDs were recruited. Compared with general workers, the participants reported a lower level of work ability and overall QOL. Work ability was significantly associated with overall QOL when covariates were controlled. Among the four domains of QOL, work ability was significantly associated with both the physical and psychological domains. The conclusion was that work ability is a definite factor of QOL for patients with WMSDs; the essence of work ability may be beyond economic function or social support. Strategies to help workers with WMSDs enhance their work ability to fit their new or temporary jobs would be beneficial to their QOL.


Subject(s)
Musculoskeletal Diseases , Quality of Life , Work Capacity Evaluation , Adult , Cross-Sectional Studies , Female , Humans , Male , Middle Aged , Musculoskeletal Diseases/complications , Surveys and Questionnaires , Taiwan , Young Adult
16.
RSC Adv ; 10(27): 15846-15852, 2020 Apr 21.
Article in English | MEDLINE | ID: mdl-35493675

ABSTRACT

In this study, hierarchically mesoporous silica (HMS) with properties such as high specific surface area, high photostability, and no cellular toxicity was synthesized. The synthesized silica can be considered as an excellent carrier candidate material. Through the use of nitrogen adsorption and desorption analysis, the shape of the hysteresis loop implied the presence of mesoporous structures in the HMS powder. In addition, the encapsulation efficiency was more than 90%. These results showed that avobenzone could be encapsulated into the HMS powder because of its high specific surface area and pore volume. Additionally, X-ray diffractometry (XRD), Fourier transform infrared spectroscopy (FTIR), thermal gravimetric analysis (TGA), and UV-visible (Vis) spectrophotometry were used to prove that the hierarchically mesoporous silica was able to effectively encapsulate avobenzone. In addition, the new synthetic sunscreen kept its excellent UVA absorption properties after being encapsulated.

17.
Cancer Genomics Proteomics ; 17(1): 61-76, 2020.
Article in English | MEDLINE | ID: mdl-31882552

ABSTRACT

BACKGROUND/AIM: In precision therapy, liposomal encapsulated chemotherapeutic drugs have been developed to treat cancers by achieving higher drug accumulation in the tumor compared to normal tissues/organs. MATERIALS AND METHODS: We developed a novel chemoradiotherapeutic approach via nanoliposomes conjugated with vinorelbine (VNB) and 111In (111In-VNB-liposome) and examined their pharmacokinetics, biodistribution, maximum tolerance dose, and toxicity in a NOD/SCID mouse model. RESULTS: Pharmacokinetic results showed that the area under the curve (AUC) of PEGylated liposomes was about 17-fold higher than that of the free radioisotope. Tumor growth inhibition by 111In-VNB-liposome was significantly higher than that of the control (p<0.05). CONCLUSION: The tumors in NOD/SCID mice bearing HT-29/tk-luc xenografts were significantly suppressed by 111In-VNB-liposomes. The study proposed repeated treatments with a novel liposome-mediated radiochemotherapy and validation of therapeutic efficacy via imaging.


Subject(s)
Chemoradiotherapy/methods , Colorectal Neoplasms/therapy , Indium Radioisotopes/pharmacology , Liposomes/administration & dosage , Multimodal Imaging/methods , Polyethylene Glycols/chemistry , Vinorelbine/pharmacology , Animals , Antineoplastic Agents, Phytogenic/pharmacokinetics , Antineoplastic Agents, Phytogenic/pharmacology , Apoptosis , Cell Proliferation , Colorectal Neoplasms/diagnostic imaging , Colorectal Neoplasms/pathology , Humans , Indium Radioisotopes/pharmacokinetics , Liposomes/chemistry , Male , Mice , Mice, Inbred NOD , Mice, SCID , Positron-Emission Tomography , Tissue Distribution , Tumor Cells, Cultured , Vinorelbine/pharmacokinetics , Whole Body Imaging , Xenograft Model Antitumor Assays
18.
Oncol Lett ; 17(1): 638-645, 2019 Jan.
Article in English | MEDLINE | ID: mdl-30655811

ABSTRACT

Trichostatin A (TSA), a hydroxamate histone deacetylase inhibitor, is a compound that has been identified to induce anticancer activity. The aim of the present study was to investigate whether sorafenib, in combination with TSA, was able to augment the anticancer effects of TSA, identifying an optimum treatment time plan and the potential underlying molecular mechanisms involved in human hepatocellular carcinoma (HCC) in vitro. Huh7/nuclear factor-κB (NF-κB)-luc2 cells were treated with TSA or sorafenib alone, or sorafenib, prior to, in combination with or following TSA treatment. Huh7/NF-κB-luc2 cell viability following TSA treatment was determined using an MTT assay, and NF-κB activity was analyzed. In addition, the expression levels of NF-κB-regulated downstream effector proteins were assayed by western blotting. Inhibitors of mitogen-activated protein kinases (MAPKs), protein kinase B (AKT) and mutant inhibitor of NF-κBα (IκBαM) vectors were used to confirm the function of the NF-κB signal transduction pathways in response to the effects of sorafenib combined with TSA against HCC. The results of the present study indicated that pre-treatment with sorafenib followed by TSA inhibited the cell viability compared with other treatment modalities, and prevented TSA-induced extracellular-signal-regulated kinase (ERK)/NF-κB activity and expression of downstream effector proteins. It was further demonstrated that IκBαM vector sensitized Huh7/NF-κB-luc2 cells to TSA, thus it was possible to reverse TSA-induced NF-κB activity using PD98059, a MAPK/ERK kinase inhibitor. In conclusion, sorafenib pre-treatment may increase the efficacy of subsequent TSA treatment in HCC. Furthermore, sorafenib pre-treatment is hypothesized to sensitize HCC to TSA via the inhibition of the MEK/ERK/NF-κB signal transduction pathway.

19.
Inflamm Res ; 67(10): 847-861, 2018 Oct.
Article in English | MEDLINE | ID: mdl-30109356

ABSTRACT

OBJECTIVE AND DESIGN: To investigate the amelioration effects of quetiapine on rheumatoid arthritis with RAW 264.7 macrophage and collagen-induced arthritis (CIA) DBA/1J mouse model. SUBJECTS: RAW 264.7 macrophage and DBA/1J mice. TREATMENT: Lipopolysaccharide and collagen. METHODS: RAW 264.7 macrophages stimulated by lipopolysaccharide (LPS) followed by quetiapine treatments were investigated. Activations of CD80 and CD86 were analyzed by flow cytometry. Pro-inflammatory cytokines such as IL-6, TNF-α and IL-1ß were analyzed by ELISA. Proteins involved in signaling pathways related to the formation of rheumatoid arthritis were assayed by Western blotting. Therapeutic efficacy of quetiapine in CIA mouse model was also assayed. 18F-FDG/micro-PET was used to monitor the inflammation status in the joints, and the severity of bone erosion was evaluated with micro-CT and H&E staining. RESULTS: The inhibition of pro-inflammatory cytokines by quetiapine was found through the ERK and AKT phosphorylation and subsequent NF-κB and CREB signaling pathways. Pro-inflammatory cytokines such as IL-17, IL-6 and IL-1ß were decreased, while immunosuppressive factors such as TGF-ß and IL-10 were increased in CIA mice treated with quetiapine. Notably, no uptake of 18F-FDG and bone erosion was found with micro-PET images on days 32 and 43 in the quetiapine-treated and normal control groups. However, significant uptake of 18F-FDG could be observed in the CIA group during the same time course. Similar results were further verified with ex vivo autoradiography. CONCLUSION: Taken together, these results suggest that quetiapine is a potential anti-inflammatory drug, and may be used as an adjuvant for the treatment of rheumatoid arthritis.


Subject(s)
Anti-Inflammatory Agents/therapeutic use , Arthritis, Experimental/drug therapy , Quetiapine Fumarate/therapeutic use , Animals , Anti-Inflammatory Agents/pharmacology , Arthritis, Experimental/metabolism , Lipopolysaccharides/pharmacology , MAP Kinase Signaling System/drug effects , Mice , Mice, Inbred DBA , Proto-Oncogene Proteins c-akt/metabolism , Quetiapine Fumarate/pharmacology , RAW 264.7 Cells
20.
Oncol Rep ; 40(3): 1390-1400, 2018 Sep.
Article in English | MEDLINE | ID: mdl-30015952

ABSTRACT

Tetrandrine (TET), a traditional Chinese clinical agent, has been used for the treatment of many diseases, including cancers. The purpose of the present study was to investigate the combined effects of TET and ionizing radiation (IR) on murine CT26 colorectal adenocarcinoma cells in vitro and in vivo. A CT26 cell line transfected with dual HSV­1 thymidine kinase and firefly luciferase (luc) reporter genes was used. The half­maximal inhibitory concentration (IC50) of TET in CT26/tk­luc cells was ~10 µM. An additive effect was observed after combination of both agents based on a colony formation assay. Apoptosis and cleaved caspase­3 levels were increased significantly in cells after combination treatment, as shown by flow cytometric analysis, DNA fragmentation and western blotting. However, tumor growth inhibition and therapeutic efficacy of TET combined with IR in vivo were identified to be synergistic, as monitored by tumor growth delay time, measured with a digital caliper. A significant inhibition of tumor growth was identified in the combination group compared with the radiation only group. Furthermore, non­invasive bioluminescent imaging (BLI) and gamma scintigraphy were also used to evaluate therapeutic efficacy. Both modalities revealed that the best tumor growth control was under combination treatment among all groups. The present study demonstrated that TET is not only beneficial for chemotherapy, but also has potential as a radiosensitizer for the treatment of cancer.


Subject(s)
Benzylisoquinolines/pharmacology , Chemoradiotherapy , Colorectal Neoplasms/therapy , Disease Models, Animal , Radiation, Ionizing , Radiation-Sensitizing Agents/pharmacology , Animals , Apoptosis/drug effects , Apoptosis/radiation effects , Cell Proliferation/drug effects , Cell Proliferation/radiation effects , Colorectal Neoplasms/pathology , Male , Mice , Mice, Inbred BALB C , Tumor Cells, Cultured
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