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1.
Front Oncol ; 11: 747123, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34745972

RESUMO

Breast carcinoma en cuirasse (CeC) is an extremely rare form of cutaneous metastases of breast cancer, characterized by diffuse sclerodermoid induration of the skin. It may be difficult to distinguish CeC from some skin diseases, including postirradiation morphea, inflammatory breast cancer, radiation dermatitis, and other cutaneous metastases, but it can be easily discerned by histology. Because of the small number of documented cases, the treatment consensus has not been clearly defined. Here, we show a 45-year-old woman with grade III infiltrating ductal carcinoma manifesting as CeC to the chest wall. Early diagnosis and treatment are essential to prevent the catastrophic natural progression of this rare malignancy.

2.
Innovation (N Y) ; 2(4): 100168, 2021 Nov 28.
Artigo em Inglês | MEDLINE | ID: mdl-34746905

RESUMO

Electro-responsive actuators (ERAs) hold great promise for cutting-edge applications in e-skins, soft robots, unmanned flight, and in vivo surgery devices due to the advantages of fast response, precise control, programmable deformation, and the ease of integration with control circuits. Recently, considering the excellent physical/chemical/mechanical properties (e.g., high carrier mobility, strong mechanical strength, outstanding thermal conductivity, high specific surface area, flexibility, and transparency), graphene and its derivatives have emerged as an appealing material in developing ERAs. In this review, we have summarized the recent advances in graphene-based ERAs. Typical the working mechanisms of graphene ERAs have been introduced. Design principles and working performance of three typical types of graphene ERAs (e.g., electrostatic actuators, electrothermal actuators, and ionic actuators) have been comprehensively summarized. Besides, emerging applications of graphene ERAs, including artificial muscles, bionic robots, human-soft actuators interaction, and other smart devices, have been reviewed. At last, the current challenges and future perspectives of graphene ERAs are discussed.

3.
Exp Neurol ; 347: 113918, 2021 Nov 05.
Artigo em Inglês | MEDLINE | ID: mdl-34748756

RESUMO

In temporal lobe epilepsy (TLE), abnormal axon guidance and synapse formation lead to sprouting of mossy fibers in the hippocampus, which is one of the most consistent pathological findings in patients and animal models with TLE. Glypican 4 (Gpc4) belongs to the heparan sulfate proteoglycan family, which play an important role in axon guidance and excitatory synapse formation. However, the role of Gpc4 in the development of mossy fibers sprouting (MFS) and its underlying mechanism remain unknown. Using a pilocarpine-induced mice model of epilepsy, we showed that Gpc4 expression was significantly increased in the stratum granulosum of the dentate gyrus at 1 week after status epilepticus (SE). Using Gpc4 overexpression or Gpc4 shRNA lentivirus to regulate the Gpc4 level in the dentate gyrus, increased or decreased levels of netrin-1, SynI, PSD-95, and Timm score were observed in the dentate gyrus, indicating a crucial role of Gpc4 in modulating the development of functional MFS. The observed effects of Gpc4 on MFS were significantly antagonized when mice were treated with L-leucine or rapamycin, an agonist or antagonist of the mammalian target of rapamycin (mTOR) signal, respectively, demonstrating that mTOR pathway is an essential requirement for Gpc4-regulated MFS. Additionally, the attenuated spontaneous recurrent seizures (SRSs) were observed during chronic stage of the disease by suppressing the Gpc4 expression after SE. Altogether, our findings demonstrate a novel control of neuronal Gpc4 on the development of MFS through the mTOR pathway after pilocarpine-induced SE. Our results also strongly suggest that Gpc4 may serve as a promising target for antiepileptic studies.

4.
Front Public Health ; 9: 769687, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34746088

RESUMO

This article takes the Guangdong Province of China as the research object and uses the difference-in-difference model to evaluate the impact of smart city construction on the quality of public occupational health and intercity differences. The obtained results show that smart city construction significantly improves the quality of public occupational health, and it is still valid after a series of robustness tests. The effect of this policy is stronger in cities that belong to the Pearl River Delta region or sub-provincial level cities. This study indicates that the central government should improve the pilot evaluation system and the performance appraisal mechanism of smart cities from the perspective of top-level design during the process of promoting smart city construction, which aims to correctly guide local governments to promote the construction of smart cities. To achieve the full improvement effect of smart city construction on the quality of public occupational health, local governments should implement smart city strategies in a purposeful and planned way according to the actual situation of the development of the jurisdiction.


Assuntos
Saúde do Trabalhador , China , Cidades , Saúde Pública , Rios
5.
Front Immunol ; 12: 738907, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34721404

RESUMO

Background: Bullous pemphigoid (BP) is an autoimmune blistering disorder that predominantly affects the elderly. As the main treatment for BP, systemic corticosteroids are often limited by their side effects. Safer treatment modalities are therefore needed. Dupilumab is a biologic agent used to treat BP in recent years. Methods: Medical records of patients with moderate-to-severe BP were retrospectively reviewed. Twenty-four patients were included (follow-up period: 32 weeks), eight of whom received dupilumab in combination with methylprednisolone and azathioprine (dupilumab group) while the other 16 patients received methylprednisolone and azathioprine (conventional group). Response to dupilumab was evaluated by comparison of several parameters (time to stop new blister formation, time to reduce the systemic glucocorticoids to minimal dose, and total amount of methylprednisolone). Results: The median age of patients in the dupilumab and conventional groups were 64.50 years (range: 22-90 years) and 64.50 years (range: 17-86 years), respectively. The median duration of disease before admission in the dupilumab group was 2 months (range: 1-240 months) and 2.5 months (range: 1-60 months) in the conventional group. The median time to stop new blister formation was 8 days (range: 1-13 days) and 12 days (range: 5-21 days) in patients of the dupilumab and conventional groups, respectively (p = 0.028 by Kaplan-Meier analysis). In addition, the median time to reduce the systemic glucocorticoids to minimal dose (methylprednisolone 0.08 mg/kg/day) was 121.5 and 148.5 days for the dupilumab and conventional therapy groups, respectively (p = 0.0053 by Kaplan-Meier analysis). The median total amount of methylprednisolone (at the time of reaching the minimal dose) used in the dupilumab group was 1,898 mg (range: 1,624-2,932 mg) while the cumulative dose of conventional group was 2,344 mg (range: 1,708-4,744 mg) (p = 0.036 by Mann-Whitney U test). The median total amount of azathioprine (at the time of reaching the minimal dose) used in dupilumab group was 8,300 mg (range: 7,100-10,400 mg) while the total dose of conventional group was 10,300 mg (range: 8,900-14,400 mg) (p = 0.0048 by Mann-Whitney U test). No adverse event related to dupilumab was recorded. Conclusions: Dupilumab in addition to methylprednisolone and azathioprine seems superior to methylprednisolone/azathioprine alone in controlling disease progression and accelerating the tapering of glucocorticoids.

6.
Biomed Res Int ; 2021: 5171086, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34611527

RESUMO

As the main economic crop cultivated in the Yellow River Delta, winter jujube contains various nutrients. However, soil salinization and fungal diseases have affected the yield and quality of winter jujube. In order to use plant growth-promoting rhizobacteria (PGPR) to reduce these damages, the antagonistic bacteria CZ-6 isolated from the rhizosphere of wheat in saline soil was selected for experiment. Gene sequencing analysis identified CZ-6 as Bacillus amyloliquefaciens. In order to understand the salt tolerant and disease-resistant effects of CZ-6 strain, determination of related indicators of salt tolerance, pathogen antagonistic tests, and anti-fungal mechanism analyses was carried out. A pot experiment was conducted to evaluate the effect of CZ-6 inoculation on the rhizosphere microbial community of winter jujube. The salt tolerance test showed that CZ-6 strain can survive in a medium with a NaCl concentration of 10% and produces indole acetic acid (IAA) and 1-aminocyclopropane-1-carboxylic acid (ACC) deaminase. Studies on the inhibition mechanism of pathogenic fungi show that CZ-6 can secrete cellulase, protease, and xylanase. Gas chromatography-mass spectrometry (GC-MS) analysis showed that CZ-6 can release volatile organic compounds (VOCs), including 2-heptanone and 2-nonanone. In addition, the strain can colonize the rhizosphere and migrate to the roots, stems, and leaves of winter jujube, which is essential for plant growth or defense against pathogens. Illumina MiSeq sequencing data indicated that, compared to the control, the abundance of salt-tolerant bacteria Tausonia in the CZ-6 strain treatment group was significantly increased, while the richness of Chaetomium and Gibberella pathogens was significantly reduced. Our research shows that CZ-6 has the potential as a biological control agent in saline soil. Plant damage and economic losses caused by pathogenic fungi and salt stress are expected to be alleviated by the addition of salt-tolerant antagonistic bacteria.

7.
J Matern Fetal Neonatal Med ; : 1-12, 2021 Oct 20.
Artigo em Inglês | MEDLINE | ID: mdl-34670468

RESUMO

OBJECTIVE: Preterm birth is now a global health problem. There is a great alteration of sleep duration in pregnancy. Whether sleep duration in pregnancy affects preterm birth remains unclarified. This study aimed to examine the associations of sleep duration on preterm birth risk based on the dose-response meta-analysis. MATERIALS AND METHODS: Electronic databases (PubMed, Web of Science, and Ovid) were searched for relevant studies from database inception to September 2020. Studies describing the associations of maternal sleep duration with preterm birth risk were included. A random-effects model was adopted to calculate the summarized relative risk (SRR) and 95% confidence intervals (CIs) as the effect sizes for all studies. Moreover, dose-response analysis was used for combining studies that used categories of sleep duration as exposure. In addition, subgroup analysis and meta-regression analysis were conducted to adjust potential confounders and investigate the source of heterogeneity. RESULTS: A total of 3771 unique studies were screened, and eight cohort studies and one case-control study were identified, with a total of 2000 preterm birth cases. Pooled data indicated that extreme sleep duration (short sleep duration or long sleep duration) in pregnancy was closely related to preterm birth in comparison with normal sleep duration (SRR = 1.13, 95%CI: 1.05-1.22) and there was no significant heterogeneity among studies (I2 = 7.0%, p = .37). Begg's funnel plot failed to uncover any evidence of publication bias. The non-linearity in the association of sleep duration with preterm birth showed significance (p < .01). Considering pregnant women slept for 7 h as a reference, 4 h short sleepers had a higher predicted risk of preterm birth (RR = 1.10, 95%CI: 1.01-1.19). Additionally, as compared with women with normal sleep duration, the preterm birth risk with short sleep durations (SRR = 1.20, 95%CI: 1.05-1.37) was elevated among pregnant women, and long sleep duration was related to preterm birth after adjusting for age (SRR = 1.20, 95%CI: 1.01-1.42). CONCLUSION: There is an association of extreme sleep duration in pregnancy with preterm birth. In a non-linear dose-response meta-analysis, a U-shaped relationship between sleep duration and risk of preterm birth was observed and pregnant women who slept 4 h/day had a significantly higher risk of preterm birth than those who slept normally.

8.
Huan Jing Ke Xue ; 42(11): 5322-5332, 2021 Nov 08.
Artigo em Chinês | MEDLINE | ID: mdl-34708971

RESUMO

Health risk analysis can predict and control the risks posed by heavy metals, especially in drinking water, which is a highly sensitive environmental receptors. In order to evaluate heavy metal pollution in drinking water, the monthly average concentrations of As, Cd, Cu, Hg, Ni, and Zn were used to assess the health risk between January 2015 and December 2018 in a drinking water source. Furthermore, Spearman rank correlation coefficient and the ARIMA model were used to analyze temporal variations. The results showed that the monthly average concentrations of heavy metals exceeded the class Ⅲ values as specified by Chinese environmental quality standard for surface water(GB 3838-2002), especially Hg with a minimum monthly average four times more than that set by the standard limits. Overall, the order of carcinogenic risk of As and Cd was decreased; the non-carcinogenic risk of Zn, Cu, Ni, Pb, and Hg was increased. Further, the comprehensive non-carcinogenic risk for adults was lower than 1 throughout the study period except February 2015, when the comprehensive non-carcinogenic risk for children was lower than or close to 1 after October 2017, and the comprehensive carcinogenic risk for children was more than 10-4. Meanwhile, the children's health risks are higher than that for adults, with the main health risk characteristic factors of As, Cd, and Hg. The Spearman rank correlation coefficient were -0.714069, -0.773122, and -0.62234, indicating the significant downward trend from 2015 to 2018. However, the children's comprehensive carcinogenic risk, whose average value was 0.000234 much more than 10-4, had significant upward trend in 2018 with Spearman rank correlation coefficient 0.902098. The ARIMA(3,1,3) model was able to predict the comprehensive carcinogenic risk for children from heavy metals in drinking water, and the result indicated the children comprehensive carcinogenic risk should be monitored to ensure levels between 0.000200 and 0.000302. The study has positive significance for risk warning and environmental management compared to the analysis and prediction of health risk from heavy metals in drinking water sources based on time series models.


Assuntos
Água Potável , Metais Pesados , Poluentes Químicos da Água , Adulto , Criança , China , Água Potável/análise , Monitoramento Ambiental , Humanos , Metais Pesados/análise , Medição de Risco , Poluentes Químicos da Água/efeitos adversos , Poluentes Químicos da Água/análise
9.
World J Emerg Med ; 12(4): 261-267, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34512821

RESUMO

BACKGROUND: There is controversy regarding whether saddle main pulmonary artery (MPA) embolism represents a high risk of deterioration in non-high-risk acute pulmonary embolism (PE) patients. This study aims to address this issue by conducting a propensity score matching (PSM) study. METHODS: A total of 727 non-high-risk acute PE patients were retrospectively evaluated. We evaluated the Bova score and risk stratification to examine the risk of deterioration. Deterioration defined as any adverse event within 30 days after admission. Computed tomographic pulmonary angiography was used to identify the embolism type. All patients were matched into four subgroups by PSM according to age, sex, Bova score, and risk stratification: (1) MPA and non-MPA embolism; (2) non-saddle MPA and non-MPA embolism; (3) saddle MPA and non-saddle MPA embolism; (4) saddle MPA and non-MPA embolism. Correlations were analyzed using Cox regression analysis, and deterioration risk was compared between subgroups using Kaplan-Meier analysis. RESULTS: Cox regression analysis revealed that MPA embolism was correlated with deterioration, regardless of whether saddle MPA embolism was included or excluded. Saddle MPA embolism was not correlated with deterioration, regardless of comparison with non-saddle MPA embolism or non-MPA embolism. Patients with MPA and non-saddle MPA embolism presented a high risk for deterioration (log-rank test=5.23 and 4.70, P=0.022 and 0.030, respetively), while patients with saddle MPA embolism were not at a high risk of deterioration (log-rank test=1.20 and 3.17, P=0.729 and 0.077, respetively). CONCLUSIONS: Saddle MPA embolism is not indicative of a high risk of deterioration in non-high-risk acute PE patients.

10.
Clin Cosmet Investig Dermatol ; 14: 1033-1043, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34471367

RESUMO

Background: Atopic dermatitis (AD) is a chronic, inflammatory cutaneous disorder characterized by a T helper 2 (Th2) immune response phenotype. Extracellular vesicles (EVs) are a heterogeneous family of cell-derived membranous structures, which transport cellular components such as DNA and proteins, and are involved in multiple physiological and pathological processes. Increasing evidence has shown that EVs secretion took part in the pathogenesis of AD. However, the proteomic studies of plasma-derived EVs in AD patients have not been reported. Objective: In this study, we investigated the diversity of plasma EVs collected from AD patients and healthy individuals and suggested that the candidates for uniquely or differentially expressed proteins in plasma EVs could be a diagnostic marker in AD. Methods: The plasma EVs were collected from 12 patients with moderate-to-severe AD and 13 healthy subjects. Proteomic analysis was performed by using a comprehensive nanoLC­MS/MS method. Results: Proteomic analysis revealed that a total of 1478 proteins in plasma EVs were found to be common proteins in AD, whereas a total of 1597 proteins in plasma EVs were found to be common proteins in HC. Eighty-six proteins in plasma EVs showed more than 2.5-fold up-regulation, while a total of 225 proteins in plasma EVs showed less than 1/2.5-fold down-regulation with a significant difference (p < 0.05) among AD compared with HC. The candidates for differentially expressed proteins in plasma EVs have been described as a connectivity PPI network related to several KEGG pathways, including pathways in platelet activation, complement, and so on. Conclusion: SLP-76 tyrosine phosphoprotein (SLP76) involved in platelet activation may significantly contribute to the pathogenesis of AD. We will further verify the role of SLP67 in AD via animal and cell experiments to provide a promising therapeutic or diagnostic target.

11.
Artigo em Inglês | MEDLINE | ID: mdl-34478047

RESUMO

Nail psoriasis is a refractory disease that affects 50-79% skin psoriasis patients and up to 80% of patients with psoriatic arthritis (PsA). The pathogenesis of nail psoriasis is still not fully illuminated, although some peculiar inflammatory cytokines and chemokines seems to be the same as described in psoriatic skin lesions. Psoriatic nail involving matrix can cause pitting, leukonychia, red spots in lunula, and nail plate crumbling, while nail bed involvement can result in onycholysis, oil-drop discoloration, nail bed hyperkeratosis, and splinter hemorrhages. The common assessment methods of evaluating nail psoriasis includes Nail Psoriasis Severity Index (NAPSI), Nail Assessment in Psoriasis and Psoriatic Arthritis (NAPPA), Nail Psoriasis Quality of life 10 (NPQ10), and so on. Treatment of nail psoriasis should be individualized according to the number of involving nail, the affected site of nail and presence of skin and/or joint involvement. Generally, topical therapies are used for mild nail psoriasis, while biologic agents such as etanercept are considered for severe nail disease and refractory nail psoriasis. Even though the current literature has shown some support for the pathogenesis, clinical presentation, or therapies of nail psoriasis, systemic review of this multifaceted disease is still rare to date. We elaborate recent developments in nail psoriasis epidemiology, pathogenesis, anatomy, clinical manifestation, diagnosis, differential diagnosis, and therapies to raise better awareness of the complexity of nail psoriasis and the need for early diagnosis or intervention.

12.
Anal Bioanal Chem ; 413(26): 6671-6676, 2021 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-34523013

RESUMO

Polymerase chain reaction (PCR) technology has become a standard technique for the detection of genetically modified organisms (GMOs). However, this method requires a PCR amplification process which is both expensive and time-consuming. Herein, we propose electric field-induced release and measurement (EFIRM) technology as an alternative method for GMO screening. The specificity and sensitivity of the EFIRM assay were proven to be comparable to those of the real-time PCR method for detecting genetically modified soybeans. After all the parameters had been evaluated, the actual evaluation of soybean samples from soybean cargoes was performed. An actual EFIRM screening was performed on 157 soybean cargo samples, which had 102 transgenic soybean samples containing the GTS-40-3-2 gene, through a blind trial at the Dalian port of China. Our results showed that 101 transgenic soybean samples were correctly detected, with only one false-negative case, and 55 non-transgenic soybean samples were detected as negative; this demonstrates that the EFIRM assay is an effective, accurate, simple, and economical novel method for detecting transgenic products, which may have a positive impact on the development of rapid on-site GMO monitoring platforms.

13.
Australas J Dermatol ; 62(4): e586-e588, 2021 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-34570365

RESUMO

Malignant atrophic papulosis (Degos disease) is a rare syndrome of multiple-system vascular diseases with unknown etiology. It can affect the skin, gastrointestinal tract and central nervous system. Here, we report a 58-year-old woman with extensive porcelain-white atrophic papules. Based on the clinical manifestations, skin biopsy and colonoscopy, a diagnosis of malignant atrophic papulosis was confirmed.

14.
Cells ; 10(9)2021 09 08.
Artigo em Inglês | MEDLINE | ID: mdl-34571998

RESUMO

The bacterial microbiota in the skin and intestine of patients with psoriasis were different compared with that of healthy individuals. However, the presence of a distinct blood microbiome in patients with psoriasis is yet to be investigated. In this study, we investigated the differences in bacterial communities in plasma-derived extracellular vesicles (EVs) between patients with moderate to severe psoriasis (PSOs) and healthy controls (HCs). The plasma EVs from the PSO (PASI > 10) (n = 20) and HC (n = 8) groups were obtained via a series of centrifugations, and patterns were examined and confirmed using transmission electron microscopy (TEM) and EV-specific markers. The taxonomic composition of the microbiota was determined by using full-length 16S ribosomal RNA gene sequencing. The PSO group had lower bacterial diversity and richness compared with HC group. Principal coordinate analysis (PCoA)-based clustering was used to assess diversity and validated dysbiosis for both groups. Differences at the level of amplicon sequence variant (ASV) were observed, suggesting alterations in specific ASVs according to health conditions. The HC group had higher levels of the phylum Firmicutes and Fusobacteria than in the PSO group. The order Lactobacillales, family Brucellaceae, genera Streptococcus, and species Kingella oralis and Aquabacterium parvum were highly abundant in the HC group compared with the PSO group. Conversely, the order Bacillales and the genera Staphylococcus and Sphihgomonas, as well as Ralstonia insidiosa, were more abundant in the PSO group. We further predicted the microbiota functional capacities, which revealed significant differences between the PSO and HC groups. In addition to previous studies on microbiome changes in the skin and gut, we demonstrated compositional differences in the microbe-derived EVs in the plasma of PSO patients. Plasma EVs could be an indicator for assessing the composition of the microbiome of PSO patients.


Assuntos
Vesículas Extracelulares/microbiologia , Microbiota/genética , Psoríase/microbiologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Bactérias/genética , Disbiose/microbiologia , Feminino , Humanos , Masculino , Metagenômica/métodos , Pessoa de Meia-Idade , Pele/microbiologia , Adulto Jovem
15.
Front Public Health ; 9: 706524, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34490189

RESUMO

Background: Peak expiratory flow (PEF), as an essential index used for screening and monitoring asthma, chronic obstructive pulmonary disease, and respiratory mortality especially in the elderly, is recommended for low-resource settings in low- and middle-income countries. However, few studies have focused on the reference of PEF in China, especially in middle-aged and elderly people. Thus, this study aimed to determine age- and sex-specific reference values of PEF in the middle-aged and elderly Chinese population. Methods: There were 8,914 participants who were included for risk factor analysis and 5,498 participants included for reference value analysis. The PEF was measured using a peak flow meter in liters per minute. The distributions of standardized PEF terciles stratified by sex and age were reported. Multiple linear regression analysis was used to determine the associations between risk factors and PEF. Results: The PEF was higher in men than women across all age subgroups. The value of PEF decreased with age in both men and women. Height, weight, handgrip strength, and residence in rural were positively associated with PEF. Age and smoking status were negatively associated with PEF significantly in both men and women (P < 0.05). The mean PEF values were 367.10 and 253.00 L/min for men and women, respectively. Meanwhile, the prevalence of low PEF was 3.94 and 3.32% for men and women, respectively. Conclusions: Age- and sex-specific centiles of standardized PEF for the middle-aged and elderly Chinese population were estimated. The reference values for low PEF could provide reference standards for epidemiological studies and clinical practices in the future. Interventions to improve lung functions or to prevent respiratory disease should be paid more attention to factors associated with PEF.


Assuntos
Força da Mão , Idoso , China/epidemiologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Pico do Fluxo Expiratório , Valores de Referência , Testes de Função Respiratória
16.
Australas J Dermatol ; 2021 Aug 31.
Artigo em Inglês | MEDLINE | ID: mdl-34463968

RESUMO

Pembrolizumab is a humanised therapeutic antibody against the PD-1 receptor. It has been used in various advanced cancer immunotherapies. Here, we report an extremely rare case of a 32-year-old man who developed Stevens-Johnson syndrome (SJS) with porokeratosis simultaneously during pembrolizumab treatment for primary hepatocellular carcinoma (T3N1M1).

17.
Sheng Li Xue Bao ; 73(4): 571-576, 2021 Aug 25.
Artigo em Chinês | MEDLINE | ID: mdl-34405213

RESUMO

This study aims to explore the effects of arachidonic acid lipoxygenase metabolism in vascular calcification. We used 5/6 nephrectomy and high-phosphorus feeding to establish a model of vascular calcification in mice. Six weeks after nephrectomy surgery, vascular calcium content was measured, and Alizarin Red S and Von Kossa staining were applied to detect calcium deposition in aortic arch. Control aortas and calcified aortas were collected for mass spectrometry detection of arachidonic acid metabolites, and active molecules in lipoxygenase pathway were analyzed. Real-time quantitative PCR was used to detect changes in the expression of lipoxygenase in calcified aortas. Lipoxygenase inhibitor was used to clarify the effect of lipoxygenase metabolic pathways on vascular calcification. The results showed that 6 weeks after nephrectomy surgery, the aortic calcium content of the surgery group was significantly higher than that of the sham group (P < 0.05). Alizarin Red S staining and Von Kossa staining showed obvious calcium deposition in aortic arch from surgery group, indicating formation of vascular calcification. Nine arachidonic acid lipoxygenase metabolites were quantitated using liquid chromatography/mass spectrometry (LC-MS) analysis. The content of multiple metabolites (12-HETE, 11-HETE, 15-HETE, etc.) was significantly increased in calcified aortas, and the most abundant and up-regulated metabolite was 12-HETE. Furthermore, we examined the mRNA levels of metabolic enzymes that produce 12-HETE in calcified blood vessels and found the expression of arachidonate lipoxygenase-15 (Alox15) was increased. Blocking Alox15/12-HETE by Alox15 specific inhibitor PD146176 significantly decreased the plasma 12-HETE content, promoted calcium deposition in aortic arch and increased vascular calcium content. These results suggest that the metabolism of arachidonic acid lipoxygenase is activated in calcified aorta, and the Alox15/12-HETE signaling pathway may play a protective role in vascular calcification.


Assuntos
Ácidos Hidroxieicosatetraenoicos , Calcificação Vascular , Ácido 12-Hidroxi-5,8,10,14-Eicosatetraenoico , Animais , Araquidonato 12-Lipoxigenase , Araquidonato 15-Lipoxigenase/metabolismo , Ácido Araquidônico , Lipoxigenase/metabolismo , Camundongos , Transdução de Sinais
18.
Small ; 17(37): e2102035, 2021 09.
Artigo em Inglês | MEDLINE | ID: mdl-34337863

RESUMO

Radiation dermatitis is a common but torturous side effect during radiotherapy, which greatly decreases the life quality of patients and potentially results in detrimental cessation of tumor treatment. Fullerenol, known as "free radical sponge," is a great choice for skin radioprotection because of its broad-spectrum free radical scavenging performance, good chemical stability, and biosafety. In this work, a facile scalable and eco-friendly synthetic method of fullerenols by catalyst assistant mechanical chemistry strategy is provided. As no organic solvent or high concentration of acid and alkali is introduced to this synthetic system, large-scale (>20 g) production of fullerenols with high yield (>95%) is obtained and no complicated purification is required. Then, the skin radioprotective performance of fullerenols is systematically explored for the first time. In vitro results indicate that fullerenols significantly block the reactive oxygen species-induced damage and enhance the viability of irradiated human keratinocyte cells. In vivo experiments suggest that medical sodium hyaluronate hydrogels loaded with fullerenols are suitable for skin administration and powerfully mitigate radiodermatitis via effectively protecting epidermal stem cells. The work not only provides an efficient gram-scale and eco-friendly synthetic method of fullerenols, but also promotes the development of fullerenols as potential skin radioprotectors.


Assuntos
Fulerenos , Radicais Livres , Humanos , Espécies Reativas de Oxigênio
20.
Am J Clin Dermatol ; 22(6): 877-889, 2021 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-34374027

RESUMO

BACKGROUND: Atopic dermatitis is a chronic, inflammatory condition causing a substantial burden to patients and caregivers. SHR0302 is an oral, highly selective, Janus kinase 1 inhibitor under investigation for inflammatory skin diseases. OBJECTIVE: The aim of this study was to investigate the efficacy and safety of SHR0302 in Chinese patients with moderate to severe atopic dermatitis. DESIGN AND SETTING: A randomized, double-blind, placebo-controlled, multicenter, phase II trial was conducted in China between October 2019 and August 2020. PARTICIPANTS: Patients (n = 105) aged 18-75 years with moderate to severe dermatitis and nonresponsive or intolerant to topical or conventional systemic treatments were included. INTERVENTIONS: Patients were randomly assigned in a ratio of 1:1:1 to receive SHR0302 4 mg once daily, SHR0302 8 mg once daily, or placebo for 12 weeks. MAIN OUTCOME MEASURES: The primary efficacy endpoint was the proportion of patients achieving Investigator's Global Assessment (IGA) response (IGA of 0 [clear] or 1 [almost clear] with improvement of ≥2 grades) at week 12. Secondary efficacy assessments included Eczema Area and Severity Index (EASI) and pruritus Numerical Rating Scale (NRS) scores. RESULTS: At week 12, IGA response was achieved in nine patients (25.7%; 90% confidence interval [CI] 13.6-37.9%; p = 0.022) in the SHR0302 4 mg group, 19 patients (54.3%; 90% CI 40.4-68.1%; p < 0.001) in the SHR0302 8 mg group, and two patients (5.7%; 90% CI 0.0-12.2%) in the placebo group. EASI75 was achieved in 51.4% (p = 0.013), 74.3% (p < 0.001), and 22.9% of patients in the SHR0302 4 mg, SHR0302 8 mg, and placebo groups, respectively, while an NRS ≥3-point improvement occurred in 65.7% (p < 0.001), 74.3% (p < 0.001), and 22.9% of patients, respectively. Treatment-emergent adverse events were reported in 60.0%, 68.6%, and 51.4% of patients in the SHR0302 4 mg, SHR0302 8 mg, and placebo groups, respectively. The adverse events were mild in most cases. Three serious adverse events were reported, all being worsening of atopic dermatitis. No serious infection was reported. CONCLUSIONS AND RELEVANCE: Oral SHR0302 was effective and well tolerated in Chinese adult patients with moderate to severe atopic dermatitis. TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT04162899; URL: https://clinicaltrials.gov/ . Date first registered: 14 November 2019.

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