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1.
BMC Pulm Med ; 21(1): 145, 2021 May 03.
Artigo em Inglês | MEDLINE | ID: mdl-33941141

RESUMO

BACKGROUND: Pirfenidone is an anti-fibrotic agent shown to slow the progression of idiopathic pulmonary fibrosis (IPF). However, its effectiveness in association with serological autoimmune features in IPF remains unclear. METHODS: We retrospectively reviewed the medical records of patients with IPF treated at a tertiary care hospital in South Korea. The autoantibody status was defined as positive if we detected autoantibodies meeting the serological domain criteria for interstitial pneumonia with autoimmune features or anti-neutrophil cytoplasmic antibodies. RESULTS: We included 142 patients with IPF treated with pirfenidone for over six months (93 were autoantibody-positive and 49 were autoantibody-negative). The mean age was 69.5 ± 7.3 years, and 77.5% of the patients were male. The adjusted mean changes over one year were - 34.4 and - 112.2 mL (p = 0.168) in forced vital capacity (FVC), and - 0.53 and - 0.72 mL/mmHg/min (p = 0.356) in the lungs diffusion capacity for carbon monoxide (DLCO) in the autoantibody-negative and autoantibody-positive groups, respectively. CONCLUSIONS: Reductions in FVC and DLCO were similar in autoantibody-positive and autoantibody-negative patients with IPF treated with pirfenidone. Pirfenidone is effective in attenuating the progression of IPF, irrespective of the autoantibody status.

2.
Bioresour Technol ; 332: 125100, 2021 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-33838453

RESUMO

To investigate how the seed microbial community structure affects the improvement of methanogenesis efficiency through direct interspecies electron transfer (DIET), a biomethane potential (BMP) test was conducted using sludge collected from a total of six anaerobic digesters. DIET-stimulating microbial populations were investigated by 16S rRNA gene sequence analysis. Correlations between microbial community composition and methane production performance by DIET were analyzed. The methane production rate increased under all conditions when granular activated carbon (GAC) was injected regardless of the inoculum type. However, redundancy analysis indicated a significant correlation between the inoculum microbial community and lag time. In a network analysis, Methanolinea species distributed in the inocula formed a single modularity with lag time, suggesting that the methanogens in the inocula might reduce the lag time of methanogenesis through DIET. Overall, this study revealed that the inoculum microbial community composition is an important factor affecting methane production efficiency by DIET.


Assuntos
Metano , Microbiota , Anaerobiose , Reatores Biológicos , Transporte de Elétrons , Elétrons , RNA Ribossômico 16S/genética
3.
J Korean Med Sci ; 36(16): e106, 2021 Apr 26.
Artigo em Inglês | MEDLINE | ID: mdl-33904262

RESUMO

BACKGROUND: There are no data on comparison between clopidogrel monotherapy and prolonged dual antiplatelet therapy (DAPT) in patients at high-risk undergoing percutaneous coronary intervention (PCI). METHODS: Of 2,082 consecutive patients undergoing PCI using second-generation drug-eluting stent (DES), we studied 637 patients at high-risk either angiographically or clinically who received clopidogrel longer than 24 months and were event-free at 12 months after index PCI. Patients were divided into 2 groups: the clopidogrel monotherapy group and the prolonged DAPT group. The primary outcome was a composite of all-cause death, non-fatal myocardial infarction (MI), definite or probable stent thrombosis, or stroke between 12 months and 36 months after the index PCI. RESULTS: In propensity score-matched population (246 pairs), the cumulative rate of primary outcome was 4.5% in the clopidogrel monotherapy group and 4.9% in the prolonged DAPT group (hazard ratio, 1.21; 95% confidence interval, 0.54-2.75; P = 0.643). There was no significant difference in all-cause death, MI, stent thrombosis, stroke between the clopidogrel monotherapy group and the prolonged DAPT group. CONCLUSION: Compared with prolonged DAPT, clopidogrel monotherapy showed similar long-term outcomes in patients at high-risk after second-generation DES implantation.

4.
MAbs ; 13(1): 1914885, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33904380

RESUMO

Antibody-drug conjugates (ADCs) are targeted therapeutic agents that treat cancers by selective delivery of highly potent cytotoxic drugs to tumor cells via cancer-specific antibodies. However, their clinical benefit is limited by off-target toxicity and narrow therapeutic windows. To overcome these limitations, we have applied reductive alkylation to develop a new type of ADC that has cytotoxic drugs conjugated to the N-terminal of an antibody through amine bonds introduced via reductive alkylation reactions (NTERM). To test whether the NTERM-conjugated ADCs can widen therapeutic windows, we synthesized three different ADCs by conjugating trastuzumab and monomethyl auristatin-F using three different methods, and compared their stability, efficacy, and toxicity. The NTERM-conjugated ADC was more stable in vitro and in vivo than the thiol-conjugated and the lysine-conjugated ADCs. The NTERM-conjugated ADC showed lower toxicity compared to other ADCs, whereas its efficacy was comparable to that of the thiol-conjugated ADC and better than that of the lysine-conjugated ADC. These results suggest that the NTERM conjugation method could widen the therapeutic window of ADCs by enhancing its stability and reducing toxicity.

5.
PLoS One ; 16(4): e0249578, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33861786

RESUMO

INTRODUCTION AND OBJECTIVE: Ankylosing spondylitis (AS) has characteristics of spinal bone bridge and fusion. Although BMD reduction in AS may be presumed to be due to spinal inflammation, this study was designed to confirm whether immobilization of the spine due to syndesmophytes is related to BMD reduction, as immobilization itself is a risk factor for BMD reduction. METHODS: Among male patients diagnosed with AS according to the modified New York criteria, those who underwent bone density tests with quantitative computed tomography (QCT) were retrospectively analyzed through a chart review. The correlation between the presence or absence of bone bridges for each vertebral body level of the L spine confirmed with radiography and BMD confirmed with QCT was analyzed. RESULTS: A total of 47 male patients with AS were enrolled. The mean patient age was 46.8 ± 8.2 years, and the mean disease duration was 7.9 ± 6.4 years. The trabecular BMD of the lumbar spine (L1-L4) ranged from 23.1 to 158.45 mg/cm3 (mean 102.2 ± 37 mg/cm3), as measured with QCT. The lumbar BMD measurements showed that 30 patients (63.8%) had osteopenia or osteoporosis. Bone bridge formation showed a negative correlation with BMD. Low BMD was significantly correlated with bone bridge in the vertebral body (p < 0.05). Positive correlations were observed between bone bridge score and BASMI flexion score, whereas significant negative correlations were found between BMD and BASMI flexion score (p < 0.05). CONCLUSION: Decreased mobility of the vertebrae due to bone bridge formation affects the decrease in BMD in patients with AS.

6.
Heart ; 2021 Mar 23.
Artigo em Inglês | MEDLINE | ID: mdl-33758008

RESUMO

OBJECTIVE: To compare P2Y12 inhibitor monotherapy after 3-month dual antiplatelet therapy (DAPT) with 12-month DAPT according to the type of P2Y12 inhibitor in patients undergoing percutaneous coronary intervention (PCI). METHODS: The Smart Angioplasty Research Team: Comparison Between P2Y12 Antagonist Monotherapy vs Dual Antiplatelet Therapy in Patients Undergoing Implantation of Coronary Drug-Eluting Stents (SMART-CHOICE) randomised trial compared 3-month DAPT followed by P2Y12 inhibitor monotherapy with 12-month DAPT. In this trial, 2993 patients undergoing successful PCI with drug-eluting stent were enrolled in Korea. As a prespecified analysis, P2Y12 inhibitor monotherapy after 3-month DAPT versus 12-month DAPT were compared among patients receiving clopidogrel and those receiving potent P2Y12 inhibitor (ticagrelor or prasugrel), respectively. The primary endpoint was a composite of all-cause death, myocardial infarction or stroke at 12 months after the index procedure. RESULTS: Among 2993 patients (mean age 64 years), 58.2% presented with acute coronary syndrome. Clopidogrel was prescribed in 2312 patients (77.2%) and a potent P2Y12 inhibitor in 681 (22.8%). There were no significant differences in the primary endpoint between the P2Y12 inhibitor monotherapy group and the DAPT group among patients receiving clopidogrel (3.0% vs 3.0%; HR: 1.02; 95% CI 0.64 to 1.65; p=0.93) as well as among patients receiving potent P2Y12 inhibitors (2.4% vs 0.7%; HR: 3.37; 95% CI 0.77 to 14.78; p=0.11; interaction p=0.1). Among patients receiving clopidogrel, P2Y12 inhibitor monotherapy compared with DAPT showed consistent treatment effects across various subgroups for the primary endpoint. Among patients receiving potent P2Y12 inhibitors, the rate of bleeding (Bleeding Academic Research Consortium types 2- 5) was significantly lower in the P2Y12 inhibitor monotherapy group than in the DAPT group (1.5% vs 5.0%; HR: 0.33; 95% CI 0.12 to 0.87; p=0.03). CONCLUSIONS: Compared with 12-month DAPT, clopidogrel monotherapy after 3-month DAPT showed comparable cardiovascular outcomes in patients undergoing PCI. TRIAL REGISTRATION NUMBER: NCT02079194.

7.
J Am Heart Assoc ; 10(6): e019022, 2021 Mar 16.
Artigo em Inglês | MEDLINE | ID: mdl-33660515

RESUMO

Background As an initial treatment strategy, percutaneous coronary intervention (PCI) for coronary chronic total occlusion (CTO) did not show midterm survival benefits compared with optimal medical therapy (OMT). We sought to evaluate the benefit of PCI compared with OMT in patients with CTO over extended long-term follow-up. Methods and Results Between March 2003 and February 2012, 2024 patients with CTO were enrolled in a single-center registry and followed for ≈10 years. We excluded patients with CTO who underwent coronary artery bypass graft (n=477) and classified patients into the CTO-PCI group (n=883) or OMT group (n=664) according to initial treatment strategy. Patients with multivessel disease received PCI for obstructive non-CTO lesions in both groups. In the CTO-PCI group, 699 patients (79.2%) underwent successful revascularization. The CTO-PCI group had a lower 10-year rate of cardiac death (10.4% versus 22.3%; hazard ratio [HR], 0.44 [95% CI, 0.32-0.59]; P<0.001) than the OMT group. After propensity score matching analyses, the CTO-PCI group had a lower 10-year rate of cardiac death (13.6% versus 20.8%; HR, 0.64 [95% CI, 0.45-0.91]; P=0.01) than the OMT group. The relative reduction in cardiac death at 10 years was mainly driven by a relative reduction between 3 and 10 years (8.3% versus 16.6%; HR, 0.43 [95% CI, 0.27-0.71]; P<0.001) but not at 3 years (5.7% versus 5.0%; HR, 1.12 [95% CI, 0.63-2.00]; P=0.71). The beneficial effects of CTO-PCI were consistent among subgroups. Conclusions As an initial treatment strategy, CTO-PCI might reduce late cardiac death compared with OMT in patients with CTO. Extended follow-up of randomized trials may confirm the findings of the present study.

8.
Sci Rep ; 11(1): 5762, 2021 Mar 11.
Artigo em Inglês | MEDLINE | ID: mdl-33707643

RESUMO

Interstitial lung disease (ILD), particularly idiopathic pulmonary fibrosis (IPF), has a poor prognosis. Corticosteroids are widely used in the treatment of acute exacerbation of ILD (AE-ILD). This study aimed to clarify the causes of AE-ILD, determine the efficacy of corticosteroids for treating AE-ILD, and detect differences in the mortality rate among subgroups of ILD. This was an observational retrospective single-center study. Patients with ILD who presented to the emergency department with acute respiratory symptoms from January 1, 2016, to December 31, 2018, were included. Patients with AE-ILD were classified into two groups depending on the prednisolone dose: low dose (0 to 1.0 mg/kg) or high dose (> 1.0 mg/kg). Mortality rates between patients with and without IPF were compared. This study included 182 patients with AE-ILD, including IPF (n = 117) and non-IPF (n = 65). Multivariate Cox regression analysis showed that corticosteroid dose (HR: 0.221, CI: 0.102-0.408, P < 0.001), initial P/F ratio (HR:0.995, CI:0.992-0.999, P = 0.006), and mechanical ventilation within 3 days of hospitalization (HR:4.205, CI:2.059-8.589, P < 0.001) were independent risk factors for mortality in patients with AE-ILD. This study showed that outcomes improve with higher doses of corticosteroids (> 1 mg/kg prednisolone) in patients with AE-non-IPF-ILD. However, this was not the case in patients with AE-IPF.

9.
Nanoscale Res Lett ; 16(1): 53, 2021 Mar 31.
Artigo em Inglês | MEDLINE | ID: mdl-33788062

RESUMO

Researches proving methods for nano-encapsulation of neonatal porcine islet-like cell clusters (NPCCs) using polymersomes (PSomes) formed using polymers of polyethylene glycol-block-poly lactide. Herein, our studies present efficient nano-encapsulation procedure with minimal damage and loss of NPCCs.We used N-hydroxysuccinimide (NHS) on the N-terminal of PSomes to induce binding of amine groups in the extracellular matrix surrounding NPCCs. F-10 culture medium with bovine serum albumin was used in the nano-encapsulation procedure to minimize damage and loss of NPCCs. Finally, we induced cross-linking between bifunctional PSomes (NHS-/NH2-PSomes). F-10 culture medium containing 0.25% BSA with pH of 7.3 minimized the damage and loss of NPCCs after nano-encapsulation as compared with using basic HBSS buffer (pH 8.0). Also, we induced the efficient nano-encapsulation through conjugation of PSomes using bifunctional PSomes (NHS-/NH2-PSomes).

10.
Sci Rep ; 11(1): 2777, 2021 Feb 02.
Artigo em Inglês | MEDLINE | ID: mdl-33531571

RESUMO

There is no validated clinical biomarker for disease severity or treatment response for nontuberculous mycobacterial pulmonary disease (NTM-PD). We investigated the correlation between elevated serum carbohydrate antigen (CA) 19-9 levels and NTM-PD disease activity, defined using an imaging severity score based on chest computed tomography (CT). We retrospectively examined 79 patients with NTM-PD who underwent serum CA19-9 level assessments and chest CT less than 1 month apart. NTM-PD severity was rated using a CT-based scoring system. The correlation between the CT score and serum CA19-9 levels was evaluated. Chest CT revealed nodular bronchiectasis without cavitation in most patients (78.5%). Serum CA19-9 levels were elevated in 19 (24%) patients. Serum CA19-9 levels were positively correlated with the total CT score and bronchiectasis, bronchiolitis, cavity, and consolidation subscores. Partial correlation analysis revealed a significant positive correlation between serum CA19-9 levels and CT scores for total score and bronchiectasis, bronchiolitis, cavitation, and consolidation subscores after controlling for age, sex, and BMI. Serum CA19-9 levels were positively correlated with the CT severity score for NTM-PD. Serum CA19-9 may be useful in evaluating disease activity or therapeutic response in patients with NTM-PD.

11.
Thorac Cancer ; 12(6): 890-898, 2021 03.
Artigo em Inglês | MEDLINE | ID: mdl-33529490

RESUMO

BACKGROUND: In this study, we investigated the risk factors of acquired T790M mutation among patients with lung adenocarcinoma with epidermal growth factor receptor (EGFR) tyrosine mutation who were treated with EGFR-tyrosine kinase inhibitors (TKIs). The aim was to identify the clinical impact of rebiopsy. METHODS: This multicenter, retrospective cohort study was conducted in South Korea from January 2007 to June 2017. Patients with adenocarcinoma with EGFR mutation who underwent rebiopsy and were treated with EGFR-TKIs were included. RESULTS: Of a total of 352 patients, T790M mutation was identified in 156 (41.9%) at the time of rebiopsy. The median duration from initial biopsy to rebiopsy was 17 months. Univariate logistic regression analysis revealed associations of exon 19 deletion (odds ratio [OR], 1.643; p = 0.026), absence of L858R (OR, 0.627; p = 0.042), and previous EGFR-TKI treatment duration (OR, 1.039; p < 0.001) with T790M mutation. Previous EGFR-TKI treatment duration (OR, 3.580; p < 0.001) was independently associated with T790M mutation. A multivariate Cox proportional hazard model revealed that brain metastasis at initial diagnosis (hazard ratio, 1.390; p = 0.050) tended to be associated with T790M mutation. Among the patients with T790M mutation at rebiopsy, the osimertinib user group (n = 90) had a better one-year survival (68.7 vs. 58.3%, p = 0.048) than the osimertinib nonuser group (n = 66). CONCLUSIONS: Rebiopsy might affect the clinical course of patients with EGFR-mutant adenocarcinoma who receive EGFR-TKIs.

12.
Int J Biol Macromol ; 175: 443-450, 2021 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-33556396

RESUMO

Plant-derived polysaccharides possess potential health benefits that improve intestinal health and the immune system. Molokhia leaves have a large amount of mucilage polysaccharide; in the present study, crude polysaccharide extract was prepared from molokhia leaves. The molecular weight of molokhia leaf polysaccharide fraction (MPF) was estimated to be 51.2 × 103 Da. Polysaccharide was methylated and the structure of MPF was mainly composed of rhamnogalacturonan-I structure with side chains, such as galactans and linear glucan (starch), as shown by GC-MS analysis. To study the biofunctional effects of MPF, its prebiotic and intestinal immune-enhancing activities were assayed in vitro. MPF exhibited good prebiotic activity, as shown by its high prebiotic scores, and increased contents of total short-chain fatty acids on five probiotic strains. In addition, MPF showed immune-enhancing activity on Peyer's patches, as revealed by the high bone marrow cell proliferating activity and production of immunoglobulin A and cytokines. These results demonstrate that MPF may be a potential beneficial prebiotic and intestinal immune-enhancer, which may have wide implications in the food industry.

13.
Microbes Environ ; 36(1)2021.
Artigo em Inglês | MEDLINE | ID: mdl-33563869

RESUMO

Despite the importance of microbial communities in ecosystem functions, the mechanisms underlying the assembly of rare taxa over time are poorly understood. It remains largely unknown whether rare taxa exhibit similar assembly processes to common taxa in local communities. We herein retrieved the 16S rRNA sequences of bacteria collected bimonthly for 2 years from the Pohang wastewater treatment plant. The transient-rare taxa showed different abundance distributions from the common taxa. Transient-rare taxon assemblages also exhibited higher temporal variations than common taxon assemblages, suggesting the distinct ecological patterns of the two assemblages. A multivariate analysis revealed that environmental parameters accounted for 25.3 and 61.6% of temporal variations in the transient-rare and common taxon assemblages, respectively. The fitting of all observed taxa to a neutral community model revealed that 96.4% of the transient-rare taxa (relative abundance, 71.4%) and 73.3% of the common taxa (relative abundance, 45.6%) followed the model, suggesting that stochastic mechanisms were more important than deterministic ones in the assembly of the transient-rare taxa. Collectively, the present results indicate that the transient-rare bacterial taxa at the Pohang wastewater treatment plant differed from the common taxa in ecological patterns, suggesting that dispersal is a key process in their assembly.

14.
Artigo em Inglês | MEDLINE | ID: mdl-33547718

RESUMO

OBJECTIVE: We investigated the gender difference in the 5-year outcome after percutaneous coronary intervention (PCI) using an unselected population data. BACKGROUND: Sex-specific outcome after percutaneous coronary intervention (PCI) is not consistent among studies. METHODS: A total of 48,783 patients were enrolled from a Korean nationwide cohort of PCI in year 2011. Outcomes adjusted with age and propensity for clinical characteristics were compared. Primary outcome was 5-year cumulative incidence of all-cause death. Nonfatal major adverse clinical event (MACE) consisting of revascularization, shock, or stroke was also assessed. RESULTS: In unadjusted analysis, women were older and had higher frequency of comorbidities including hypertension, hyperlipidemia, and diabetes compared to men (p < .001, all). Women had higher 5-year death risk than men (21.8 vs. 17.3%; hazard ratio [HR] 1.29, 95% confidential interval [CI] 1.23-1.34). In propensity score-matched analysis (N = 28,924), women had lower 5-year death risk (20.2 vs. 26.1%, HR 0.75, 95% CI 0.71-0.78). This lower death risk in women was consistent in subgroup analyses of age, risk factors, and clinical diagnosis including angina or acute myocardial infarction (p < .05, all). CONCLUSIONS: Older age and more common comorbidities in women contributed to the apparent worse outcome after PCI in women. After adjusting these disadvantages, women had better outcome after PCI than men.

15.
Carbohydr Polym ; 258: 117728, 2021 Apr 15.
Artigo em Inglês | MEDLINE | ID: mdl-33593583

RESUMO

To attain eco-friendly polyurethane composites with enhanced thermal and mechanical properties, in this study, a series of cationic waterborne polyurethane (cWPU) nanocomposite films reinforced with 1-50 wt% chitin nanofiber (ChNF) loadings was fabricated by a facile aqueous dispersion casting. The microstructure, thermal and mechanical properties of the nanocomposite films were investigated by considering the loading content and the interfacial interaction of ChNF in the cWPU matrix. For the purpose, a hard/soft segmented cWPU with an average particle size of ∼151 nm in aqueous dispersion was synthesized by using poly(tetramethylene glycol), isophorone diisocyanate, N-methyldiethanolamine, and 1,4-butanediol. The FT-IR spectra confirmed the existence of specific hydrogen-bonding interactions between hydroxyl/acetyl amine/ammonium groups of ChNFs and urethane/protonated amine groups of cWPU hard segments. Accordingly, the thermal decomposition temperatures of cWPU/ChNF nanocomposite films increased with increasing the ChNF content. In addition, the storage moduli of cWPU/ChNF nanocomposite films increased significantly with the increment of ChNF content up to ∼7 wt%, which stems from the restricted chain mobility of cWPU backbones composed of semicrystalline soft segments and hard segments interacting with ChNFs via multiple hydrogen-bonding interactions.

16.
Sci Rep ; 11(1): 2596, 2021 Jan 28.
Artigo em Inglês | MEDLINE | ID: mdl-33510351

RESUMO

Idiopathic pulmonary fibrosis (IPF) is an independent risk factor for lung cancer (LC) development; however, there are currently no clinical guidelines for LC surveillance in IPF. This study aimed to investigate the cumulative incidence and survival outcomes of LC in IPF. Using the National Health Insurance Service database, including medical information on people aged ≥ 40 years between 2011 and 2016, we identified IPF patients and confirmed the presence of comorbid LC. Patients diagnosed with IPF in 2011 were washed out, and mortality data were analyzed from 2012 to 2018. A total of 7277 newly diagnosed IPF patients were identified among Korean citizens aged ≥ 40 years (about 50 million people) between 2011 and 2016. Their average age was 71.5 years and 72.8% of them were male. The prevalence of LC in the IPF cases was 6.4%. The cumulative incidence rates of LC in IPF patients who did not have LC at the time of IPF diagnosis were 1.7%, 4.7%, and 7.0%, at 1, 3, and 5 years, respectively. The median time from IPF diagnosis to LC development was 16.3 (Interquartile range, 8.2-28.8) months. The survival rate was significantly lower in the IPF with LC group than the IPF without LC group (P < 0.001). We concluded that IPF increases LC risk, and LC weakens survival outcomes in IPF. Close surveillance for LC development is mandatory for patients with IPF.

18.
J Am Acad Dermatol ; 84(6): 1619-1627, 2021 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-33508387

RESUMO

BACKGROUND: Topical calcineurin inhibitors have been used to treat vitiligo, either alone or in combination with phototherapy; however, the long-term safety of these agents remains controversial. OBJECTIVE: To investigate the risk of lymphoma and skin cancer in vitiligo patients who received topical calcineurin inhibitors or phototherapy. METHODS: A multicenter retrospective cohort study of 25,694 vitiligo patients who received topical calcineurin inhibitors or phototherapy for 6 weeks or more between 2001 and 2019 was performed. Cumulative doses of topical calcineurin inhibitors and total phototherapy sessions were determined. Outcomes were the development of lymphoma or skin cancer after enrollment, confirmed through chart review and pathology reports. RESULTS: During 95,203 person-years, 13 cases of lymphoma, 22 of actinic keratosis, 15 of nonmelanoma skin cancer, and 5 of melanoma were observed. The risk of lymphoma and skin cancer was not significantly increased by topical calcineurin inhibitor dose or phototherapy sessions. The interaction between the topical calcineurin inhibitors and phototherapy was not associated with an increased risk of skin cancer. LIMITATIONS: Retrospective study, individual follow-up duration less than 4 years, and no adjustment for comorbidities and medication history. Not generalizable to other races. CONCLUSION: The long-term risk of skin cancer or lymphoma was not associated with the use of topical calcineurin inhibitors, phototherapy, and both treatments in combination in patients with vitiligo.

19.
J Nanobiotechnology ; 19(1): 15, 2021 Jan 09.
Artigo em Inglês | MEDLINE | ID: mdl-33422063

RESUMO

BACKGROUND: There is a strong need for non-invasive and patient-friendly delivery systems of protein drugs for long-term therapy. However, oral delivery of protein drugs is a big challenge due to many barriers including instability in the gastrointestinal (GI) tract and low permeability. To overcome the absorption barriers in GI tract and improve the patient compliance, this study aimed to develop an M cell targeted-nanocomposite delivery system of protein drugs. RESULTS: An aminoclay-protein core complex (AC-Ins) was prepared by using insulin as a model protein and then sequentially coated with Ulex europaeus agglutinin 1 (UEA-1) for M-cell targeting and the pH sensitive polymer, Eudragit® L100 (EUAC-Ins). All nanoparticles were obtained with a high entrapment efficiency (> 90%) and their structural characteristics were confirmed by Fourier transform-infrared spectroscopy, energy dispersive X-ray spectroscopy, and circular dichroism. Among the developed nanoparticles, EUAC-Ins effectively suppressed drug release at pH 1.2, while rapidly released drugs at pH 6.8 due to dissolution of the outer coating layer. The conformational stability of insulin entrapped in EUAC-Ins was well maintained in the presence of proteolytic enzymes. Compared to free insulin, EUAC-Ins increased the membrane transport of insulin by 4.4-fold in M cells. In parallel, oral administration of EUAC-Ins in mice enhanced insulin uptake by 4.1-fold in the intestinal Peyer's patches and 2.6-fold in intestinal epithelium tissues with normal villi, compared to free insulin. Orally administered EUAC-Ins decreased significantly the blood glucose level in diabetic mice, while the effect of oral insulin solution was negligible. CONCLUSION: An M cell targeted-ternary nanocomposite system obtained by dual coating of the aminoclay-protein core complex with UEA-1 and a pH dependent polymer is promising as an effective oral protein delivery carrier.

20.
Nat Commun ; 12(1): 396, 2021 01 15.
Artigo em Inglês | MEDLINE | ID: mdl-33452251

RESUMO

High torsional strength fibers are of practical interest for applications such as artificial muscles, electric generators, and actuators. Herein, we maximize torsional strength by understanding, measuring, and overcoming rheological thresholds of nanocarbon (nanotube/graphene oxide) dopes. The formed fibers show enhanced structure across multiple length scales, modified hierarchy, and improved mechanical properties. In particular, the torsional properties were examined, with high shear strength (914 MPa) attributed to nanotubes but magnified by their structure, intercalating graphene sheets. This design approach has the potential to realize the hierarchical dimensional hybrids, and may also be useful to build the effective network structure of heterogeneous materials.

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