The objective of this study was to formulate a nanoparticle (NP)-eluting drug delivery stent system by a cationic electrodeposition coating technology.
Nanoparticle-mediated drug delivery systems ...(DDS) are poised to transform the development of innovative therapeutic devices. Therefore, we hypothesized that a bioabsorbable polymeric NP-eluting stent provides an efficient DDS that shows better and more prolonged delivery compared with dip-coating stent.
We prepared cationic NP encapsulated with a fluorescence marker (FITC) by emulsion solvent diffusion method, succeeded to formulate an NP-eluting stent with a novel cation electrodeposition coating technology, and compared the in vitro and in vivo characteristics of the FITC-loaded NP-eluting stent with dip-coated FITC-eluting stent and bare metal stent.
The NP was taken up stably and efficiently by cultured vascular smooth muscle cells in vitro. In a porcine coronary artery model in vivo, substantial FITC fluorescence was observed in neointimal and medial layers of the stented segments that had received the FITC-NP-eluting stent until 4 weeks. In contrast, no substantial FITC fluorescence was observed in the segments from the polymer-based FITC-eluting stent or from bare metal stent. The magnitudes of stent-induced injury, inflammation, endothelial recovery, and neointima formation were comparable between bare metal stent and NP-eluting stent groups.
Therefore, this NP-eluting stent is an efficient NP-mediated DDS that holds as an innovative platform for the delivery of less invasive nano-devices targeting cardiovascular disease.
Regorafenib is an oral multikinase inhibitor affecting angiogenesis, oncogenesis, metastasis, and tumor immunity. As a systemic treatment, it has been shown to provide survival benefits in ...hepatocellular carcinoma (HCC) patients progressing on sorafenib treatment. We report herein a case of HCC with hepatic vein tumor thrombosis protruding into the inferior vena cava (IVC-HVTT) which was successfully treated by surgery following second-line chemotherapy with regorafenib. A 79-year-old man with chronic hepatitis was diagnosed with HCC. Computed tomography revealed a solitary tumor in segments 7 and 8 and an IVC-HVTT from the right hepatic vein. Since IVC-HVTT removal is a difficult procedure, the tumor was diagnosed as unresectable, and administration of sorafenib was started. Five weeks later, the lesion had increased in size by 15.3%; subsequently, regorafenib was given as second-line therapy for 12 months. After shrinkage of the IVC-HVTT, the patient was referred to our hospital for surgery. One month after the cessation of regorafenib, an extended resection of segment 8 and total removal of the IVC-HVTT was successfully performed without using total hepatic vascular exclusion. There were no serious postoperative complications. Additionally, there has been no recurrence for about 2 years since the initial therapy.
We herein report a case of sarcomatoid carcinoma that developed in a remnant stomach. A 76-year-old male with a history of distal gastrectomy for a duodenal ulcer 28 years earlier underwent ...investigation for a tumor in the remnant stomach. An endoscopic survey showed a round elevated tumor measuring 6 cm in diameter, and a biopsy specimen suggested carcinosarcoma. A total gastrectomy of the remnant stomach was performed, and the excised tumor was identified to be a malignant neoplasm consisting of both carcinomatous and sarcomatous components. A diagnosis of sarcomatoid carcinoma was made since the epithelial markers were positive even in the mesenchymal elements of the tumor. To our knowledge, only 4 cases of sarcomatoid carcinoma of the stomach have been reported in the English literature so far.
In occupational settings, smokers may take quitting smoking seriously if they experienced long-term sick leave due to cancer or cardiovascular disease (CVD). However, no study has elucidated the ...smoking cessation rate after long-term sick leave. We examined the smoking cessation rate after long-term sick leave due to cancer and CVD in Japan. We followed 23 survivors who experienced long-term sick leave due to cancer and 39 survivors who experienced long-term sick leave due to CVD who reported smoking at the last health exam before the leave. Their smoking habits before and after the leave were self-reported. Logistic regression was used to calculate adjusted smoking cessation rates. Smoking cessation rate after long-term sick leave due to cancer was approximately 70% and that due to CVD exceeded 80%. The adjusted smoking cessation rate was 67.6% (95% confidence interval CI: 47.0, 88.2) for cancer and 80.7% (95% CI: 67.7, 93.8) for CVD. Smoking cessation rate after a longer duration of sick leave (≥60 d) tended to increase for both CVD and cancer. Although any definite conclusion cannot be drawn, the data suggest that smoking cessation rate after long-term sick leave due to CVD is slightly higher than that for cancer.
Background
Because patients on maintenance hemodialysis (HD) have an impaired immune response to pathogens, they are at higher risk of severe coronavirus disease 2019 (COVID-19). However, data on ...antibody production among HD patients with COVID-19 is scarce. Thus, we performed a retrospective cohort study evaluating severe acute respiratory syndrome coronavirus two antibody (SARS-CoV-2) production within 1 month after COVID-19 onset in hospitalized patients on HD.
Methods
SARS-CoV-2-specific immunoglobulin (Ig) G levels were quantified using an iFlash 3000 Chemiluminescence Immunoassay analyzer (Shenzhen YHLO Biotech Co., Ltd.) to detect IgG antibodies specific for the S1 subunit of the spike protein (IgG-S1). Propensity score matching was used to balance covariate distribution in HD and non-HD patients. From April 2020 to February 2021, antibody testing was performed on 161 hospitalized patients with symptomatic COVID-19. Of them, 34 HD patients were matched to 68 non-HD patients.
Results
After propensity score matching, the median levels of IgG-S1 in the HD patients at 7–13 days after symptom onset were significantly lower than in non-HD patients, especially in those with severe disease. Among all patients, those with severe disease produced lower levels of IgG-S1 at 7–13 days compared with non-severe patients.
Conclusion
COVID-19 patients with severe disease, especially those undergoing HD, had lower IgG-S1 production in the second week of the disease. Thus, the increased risk of severe COVID-19 in HD patients may be, in part, due to a slow and reduced antibody response.
Aim
Antioxidant therapy for with vitamin E appears to be effective for the treatment of nonalcoholic fatty liver disease (NAFLD). However, the mechanism of action and optimal therapeutic dosage is ...unclear. The present study was undertaken to examine whether the effects of α‐tocopherol (α‐Toc) on NAFLD are dose‐dependent in a diet‐induced obese model.
Methods
Male mice were fed standard chow, high‐fat (HF) diet, HF diet with low‐dose, or with high dose of α‐Toc supplementation. Histological findings, triglyceride content, and the levels of protein expression related to fatty acid synthesis/oxidation such as carnitine palmitoyltransferase I (CPT‐1) of liver were evaluated. In addition, 2‐tetradecylglycidic acid (TDGA), a CPT‐1 inhibitor, was administered to mice fed HF diet with low‐dose of α‐Toc. Finally, HepG2 cells in fat‐loaded environment were treated with 0–50 μM α‐Toc.
Results
Treatment of low‐dose of α‐Toc decreased HF‐induced hepatic fat accumulation, but this finding was not observed in treatment of high dose of α‐Toc. HF‐induced reduction of CPT‐1 was attenuated with low‐dose of α‐Toc but not with high dose of α‐Toc. TDGA suppressed the improvement of histological findings in liver induced by low‐dose of α‐Toc treatment. CPT‐1 expression in HepG2 cells increased in response to low‐dose of α‐Toc, but not in high dose.
Conclusions
Dual action of α‐Toc on CPT‐1 protein levels was observed. The effect of vitamin E on NAFLD may be not be dose‐dependent.
Context: Spinal cord infarction (SCI) causes gait disturbance because of paresis, spasticity, and sensory disturbance of the lower limbs. There is no effective medical treatment for SCI, and ...conventional rehabilitation alone is the main approach to helping individuals work toward independent walking. The aim of this study was to evaluate the effect of gait treatment using the Hybrid Assistive Limb (HAL) on acute SCI.
Findings: A 61-year-old female and a 62-year-old male with incomplete paraplegia participated in this study. Our study participants received gait treatment with HAL 3-4 times per week, with a total of 7-8 sessions (20 min), in addition to conventional physical therapy. The American Spinal Injury Association Impairment Scale, Lower Extremity Motor Score (LEMS), Modified Ashworth Scale (MAS), the Walking Index for Spinal Cord Injury (WISCI II), comfortable gait speed (CGS), stride, cadence, Barthel Index (BI), Functional Independence Measure (FIM), modified Rankin Scale (mRS), joint angles, and adverse effects were assessed prior to HAL treatment and post-HAL treatment. HAL facilitated intensive gait treatment in people during the acute phase after SCI. Improvements in LEMS, WISCI II, CGS, stride, cadence, BI, FIM, mRS, and joint angles were observed in both study participants. Furthermore, decreased spasticity in the gastrocnemius muscle was found in one participant as assessed by MAS.
Conclusion: Gait treatment using HAL may be beneficial for paraplegic, non-ambulatory individuals with acute SCI. HAL may be useful for intensive gait treatment without increasing spasticity.
The clustered regularly interspaced short palindromic repeat (CRISPR)/CRISPR-associated endonuclease 9 (Cas9) system is being rapidly developed for mutagenesis in higher plants. Ideally, foreign DNA ...introduced by this system is removed in the breeding of edible crops and vegetables. Here, we report an efficient generation of Cas9-free mutants lacking an allergenic gene, Gly m Bd 30K, using biolistic transformation and the CRISPR/Cas9 system. Five transgenic embryo lines were selected on the basis of hygromycin resistance. Cleaved amplified polymorphic sequence analysis detected only two different mutations in e all of the lines. These results indicate that mutations were induced in the target gene immediately after the delivery of the exogenous gene into the embryo cells. Soybean plantlets (T
plants) were regenerated from two of the transgenic embryo lines. The segregation pattern of the Cas9 gene in the T
generation, which included Cas9-free plants, revealed that a single copy number of transgene was integrated in both lines. Immunoblot analysis demonstrated that no Gly m Bd 30K protein accumulated in the Cas9-free plants. Gene expression analysis indicated that nonsense mRNA decay might have occurred in mature mutant seeds. Due to the efficient induction of inheritable mutations and the low integrated transgene copy number in the T
plants, we could remove foreign DNA easily by genetic segregation in the T
generation. Our results demonstrate that biolistic transformation of soybean embryos is useful for CRISPR/Cas9-mediated site-directed mutagenesis of soybean for human consumption.
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