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1.
Comput Biol Chem ; 92: 107481, 2021 Mar 30.
Artigo em Inglês | MEDLINE | ID: mdl-33838390

RESUMO

In this study, firstly, the pharmacophore model was established based on LAR inhibitors. ZINC database and drug-like database were screened by Hypo-1-LAR model, and the embryonic compound ZINC71414996 was obtained. Based on this compound, we designed 9 compounds. Secondly, the synthetic route of the compound was determined by consulting Reaxys and Scifinder databases, and 9 compounds (1a-1i) were synthesized by nucleophilic substitution, Suzuki reaction and so on. Meanwhile, their structures were confirmed by 1H NMR and 13C NMR. Thirdly, the Enzymatic assays was carried out, the biological evaluation of compounds 1a-1i led to the identification of a novel PTP-LAR inhibitor 1c, which displayed an IC50 value of 4.8 µM. At last, molecular dynamics simulation showed that compounds could interact strongly with the key amino acids LYS1350, LYS1352, ARG1354, TYR1355, LYS1433, ASP1435, TRP1488, ASP1490, VAL1493, SER1523, ARG1528, ARG1561, GLN1570, LYS1681, thereby inhibiting the protein activity. This study constructed the pharmacophore model of LAR protein, designed small-molecule inhibitors, conducted compound synthesis and enzyme activity screening, so as to provide a basis for searching for drug-capable lead compounds.

2.
Int J Biol Macromol ; 180: 718-728, 2021 Mar 19.
Artigo em Inglês | MEDLINE | ID: mdl-33753200

RESUMO

Signal-induced proliferation-associated protein 1 (SIPA1) is highly expressed and mainly located in the nucleus in some breast cancer cell lines and clinical tumor tissues. Previous study revealed that nuclear localization of SIPA1 is functionally involved in breast cancer metastasis in the lymphatic gland. In the current study, we identified a non-typical region (140-179aa) of SIPA1 as a novel nuclear localization region (NLR) which is crucial for translocating the proteins into the nucleus in HEK293 cells and breast cancer cells. This region contained one basic amino acid, His160, and had no common features of typical nuclear localization signals. In addition, overexpressing SIPA1 without NLR could suppress breast cancer cell proliferation but could not promote cell migration in MCF7 cells. Furthermore, we found that a high expression of SIPA1 upregulated the expression of ABCB1, encoding multi-drug resistance protein MDR1, and promoted the resistance to epirubicin in breast cancer cells, while this effect was largely abolished in the cells with the expression of NLR-deleted SIPA1. This study overall, identified a nuclear localization-dependent region determining the nuclear distribution of SIPA1 and its regulation on epirubicin-sensitivity in breast cancer cells, which could be a potential drug target to facilitate the development of breast cancer chemotherapy.

3.
Sci Total Environ ; 772: 145475, 2021 Jun 10.
Artigo em Inglês | MEDLINE | ID: mdl-33770885

RESUMO

Electronic cigarettes (E-cigarette) are an alternative for traditional cigarette smokers to quit smoking. Based on the current understanding, electronic cigarettes have rapidly become popular among existing smokers and former non-smokers. However, increasing research at different levels reveals that e-cigarettes are unsafe. This review provides an overview of the toxicology of e-cigarettes based on existing in vivo and in vitro studies and compares their toxicity with that of traditional cigarettes. Moreover, we describe the associated toxicity components in e-cigarettes, as well as the potential mechanism by which e-cigarettes exert toxic effects. As is known to all, the nicotine in traditional cigarettes and e-cigarettes has certain toxicity. Besides, a few studies have shown that propylene glycol and vegetable glycerin mixture and flavoring agents in e-cigarettes also are the key components causing adverse effects in animals or cells. There is insufficient scientific evidence on the toxicity of e-cigarettes due to the lack of standardized research methods, prompting the need to conduct a comprehensive toxicity assessment of e-cigarette toxicity to elucidate the safety issues of e-cigarettes. Eventually, a basis for decision-making on whether people use e-cigarettes will be obtained.


Assuntos
Sistemas Eletrônicos de Liberação de Nicotina , Produtos do Tabaco , Animais , Glicerol , Nicotina/toxicidade , Fumar
4.
PLoS One ; 16(3): e0234855, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33725021

RESUMO

This study aimed to investigate the knowledge, practices, and attitudes of medical professionals toward Traditional Chinese Medicine (TCM) for the prevention and treatment of coronavirus disease 2019 (COVID-19). All 401 medical professionals were surveyed using an anonymous with an investigator using the Questionnaire star APP. The participants answered 14 questions; of the 401 participants, 55.2% agreed with the statement "TCM can be used for the prevention and treatment of COVID-19," 40.4% remained neutral, and 4.4% disagreed. Moreover, 75.3% agreed with the statement "There is no specific drug for COVID-19," 67% agreed with the statement "TCM can develop immunity to COVID-19" and 62.1% agreed with "TCM can alleviate the symptoms of patients with COVID-19." Meanwhile, 69.1% were aware that TCM has been recommended for COVID-19 by the National Health Commission of the People's Republic of China. Regarding the selection of sources of knowledge on whether "TCM can be used for the prevention and treatment of COVID-19," There were 277, 123, 82, 369, and 17 participants selected sources from "Hospital training," "Academic journals," "Academic Conferences," "Social media platforms (such as WeChat)" and "Others," respectively. Further, 358 participants will take TCM for the prevention of COVID-19. Multiple logistic regression analysis showed that age, major and received TCM treatment within the last five years were independent factors affecting the participants' attitudes. In the absence of specific drugs for COVID-19, more than half of the participants agreed that TCM could be used for the prevention and treatment of COVID-19 and most participants are willing to take TCM to prevent COVID-19, although unsure about its effectiveness. The main information sources on TCM for the treatment and prevention of COVID-19 were social platforms and hospital training.


Assuntos
Atitude , Conhecimento , Medicina Tradicional Chinesa , Prática Profissional , Profissionalismo , Adulto , /patologia , China , Medicamentos de Ervas Chinesas/uso terapêutico , Feminino , Humanos , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Mídias Sociais , Inquéritos e Questionários , Adulto Jovem
5.
Eur J Dermatol ; 31(1): 32-40, 2021 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-33648912

RESUMO

BACKGROUND: Acne vulgaris is a common pilosebaceous disease associated with Propionibacterium acnes (P. acnes). Resolution of comedones may occur in association with shrunken sebaceous glands (SGs) containing de-differentiated cells, however the role of P. acnes is unclear. OBJECTIVES: To investigate the effects of P. acnes on aryl hydrocarbon receptor (AhR) activation, lipogenesis and differentiation in cultured immortalized human SZ95 sebocytes. MATERIALS & METHODS: Cultured sebocytes were incubated with formalin-killed (f-) P. acnes (f-P. acnes) at different ratios of multiplicity of infection. The mRNA levels of the AhR downstream cytochrome P450 (CYP) genes were measured by quantitative RT-PCR, nuclear translocation of AhR by western blot and immunofluorescence, lipogenesis and keratinization by gene set enrichment analysis (GSEA), lipid related analysis by Oil red O staining and Nile red staining, and sebaceous differentiation-related gene expression by western blot. RESULTS: f-P. acnes upregulated CYPs mRNA levels and induced translocation of AhR protein from the cytoplasm into the nucleus. GSEA revealed downregulation of lipogenesis and upregulation of keratinization. f-P. acnes inhibited linoleic acid-induced neutral lipid synthesis and expression of sebocyte markers, keratin 7 and mucin1/EMA, but increased expression of keratinocyte markers, keratin 10 and involucrin, which were abolished by AhR gene silencing. Inhibition of lipogenesis-related genes, such as sterol response element-binding protein, was also observed. CONCLUSION: f-P. acnes inhibits lipogenesis and induces terminal differentiation of sebocytes, into keratinocyte-like cells, via activation of the AhR pathway in vitro, suggesting that follicular P. acnes is not only acnegenic but also promotes acne remission through feedback regulation of sebum production.

6.
Vet Immunol Immunopathol ; 235: 110201, 2021 Feb 06.
Artigo em Inglês | MEDLINE | ID: mdl-33735822

RESUMO

Among bloodsucking arthropods, hard tick is a vector of transmitting the most diverse human and animal pathogens, leading to an increasing number of manifestations worldwide. The development of the anti-tick vaccine has the potential to be an environmentally friendly and cost-effective option for tick management. We have previously demonstrated the induction of both humoral and cellular response against Hyalomma asiaticum (H. asiaticum) following immunization with recombinant cathepsin L-like cysteine protease from H. asiaticum tick (rHasCPL), and could control tick infestations. Interferon-gamma (IFN-γ), is an immunomodulatory factor that plays an important role in the regulation of adaptive immunity against infection. In the present study, recombinant BALB/c mouse IFN-γ (rMus-IFN-γ) was cloned and expressed using a prokaryotic expression system, and verified by Western blotting and IFN-γ-ELISA kit analysis. Female BALB/c mice (n = 12) were used for immunization using rHasCPL (100 µg) plus IFN-γ as adjuvant (10 µg). In immunized female BALB/c mice, the levels of anti-CPL antibodies as well as cytokines were determined using ELISA analysis. Protective efficacy of immunization was evaluated by larvae H. asiaticum challenge of immunized female BALB/c mice. Using rMus-IFN-γ as an adjuvant to rHasCPL vaccine (CPL + IFN-γ) promoted specific antibody IgG (IgG1 > IgG2a) and increased production of IFN-γ and IL-4 compared to immune rHasCPL group (CPL). The protected rate of immunized mice from tick challenge was significantly higher after immunization with CPL + IFN-γ (85.11 %) than with CPL (63.28 %). Immunization using CPL + IFN-γ promoted the activation of anti-HasCPL humoral and cellular immune responses, and could provide better protection against H. asiaticum infestation. This approach may could help develop a candidate vaccine for control tick infestations.

7.
J Affect Disord ; 287: 138-144, 2021 Mar 04.
Artigo em Inglês | MEDLINE | ID: mdl-33780829

RESUMO

BACKGROUND: The predictive effects of change patterns of sleep problems on mental health after a long-term disaster remain poorly known. We examined the change patterns of sleep problems after the Wenchuan earthquake, and tested whether specific sleep-related change patterns could predict mental health problems (posttraumatic stress disorder [PTSD], anxiety, and depression) in the 10 years after Wenchuan earthquake. METHODS: 1357 adolescents exposed to the Wenchuan earthquake were surveyed on potential sleep problems at 18 months (T18m) and 30 months (T30m) post-earthquake. Among them, 799 participants completed the followed-up survey online 10 years after the earthquake (T10y). Since some participants did not provide sleep problems data at both T18m and T30m, 707 samples were included in final analyses. Linear regression analysis was performed. RESULTS: Four different patterns of sleep problems were identified: stable-low pattern (61.1%), stable-high pattern (15.3%), decreasing pattern (13.2%), and increasing pattern (10.5%). Additionally, we found that individuals in stable-high and increasing patterns were more likely to experience PTSD, anxiety, and depression at T10y in the crude model. After controlling for confounders (e.g., earthquake exposure), these patterns were strongly predictive of depression at T10y. LIMITATIONS: Only two waves of sleep problems were collected and subjective sleep outcomes methods were used to collect data instead of objective methods. CONCLUSIONS: Sleep problems had heterogeneity after a deadly earthquake. Individuals in stable-high and increasing patterns should be given more attention. Timely assessment and targeted interventions on specific sleep problems are necessary for preventing an escalation of adverse mental health outcomes.

8.
J Biomed Nanotechnol ; 17(2): 205-215, 2021 Feb 28.
Artigo em Inglês | MEDLINE | ID: mdl-33785092

RESUMO

Imaging-guided cancer theranostic is a promising strategy for cancer diagnostic and therapeutic. Photodynamic therapy (PDT), as an approved treatment modality, is limited by the poor solubility and dispersion of photosensitizers (PS) in biological fluids. Herein, it is demonstrated that superparamagnetic iron oxide (SPIO)-based nanoparticles (SCFs), prepared by conjugated with Chlorin e6 (Ce6) and modified with folic acid (FA) on the surface, can be used as versatile drug delivery vehicles for effective PDT. The nanoparticles are great carriers for photosensitizer Ce6 with an extremely high loading efficiency. In vitro fluorescence imaging and in vivo magnetic resonance imaging (MRI) results indicated that SCFs selectively accumulated in tumor cells. Under near-infrared laser irradiation, SCFs were confirmed to be capable of inducing low cell viability of RM-1 cells In vitro and displaying efficient tumor ablation with negligible side effects in tumor-bearing mice models.


Assuntos
Nanopartículas , Fotoquimioterapia , Porfirinas , Animais , Linhagem Celular Tumoral , Compostos Férricos , Ácido Fólico , Imagem por Ressonância Magnética , Camundongos , Camundongos Endogâmicos BALB C , Fármacos Fotossensibilizantes/farmacologia , Medicina de Precisão , Nanomedicina Teranóstica
9.
BMC Neurol ; 21(1): 137, 2021 Mar 27.
Artigo em Inglês | MEDLINE | ID: mdl-33773590

RESUMO

BACKGROUND: Pneumonia is related to poor prognosis in acute ischemic stroke (AIS), and its risk might be higher in atrial fibrillation (AF) related AIS with elevated plasma D-dimer. The aim of our study was to investigate the prognostic value of D-dimer for predicting clinical outcome of AF-related AIS with pneumonia. METHOD: AF-related AIS patients with pneumonia were prospectively enrolled. Receiver operating characteristic (ROC) curve was used to determine the optimal D-dimer point for 3-month mortality and death/severe disability. The associations between the D-dimer and 3-month mortality and death/severe disability were assessed by multivariable logistic regression analysis. RESULTS: A total of 415 patients were enrolled in this study. ROC curve analysis showed that the optimal cut point of D-dimer for 3-month death/severe disability and mortality were D-dimer≥2.35 mg/l and D-dimer≥3.35 mg/l, respectively. Multivariable logistic regression analysis showed that D-dimer≥2.35 mg/l [adjusted odds ratio (aOR) 5.99, 95% confidence interval (CI): 3.04-11.83, P<0.001], higher NIHISS score (aOR:1.53, 95% CI: 1.38-1.69, P<0.001) and larger infarct volume (aOR 1.01, 95% CI: 1.01-1.02, P<0.001) were associated with increased risk of 3-month death/severe disability), and anticoagulant was associated with decreased risk of death/severe disability (aOR:0.21, 95% CI: 0.09-0.47, P<0.001). Higher NIHISS score (aOR:1.64, 95% CI: 1.38-1.94, P<0.001), older age (aOR 1.08, 95% CI: 1.02-1.14, P = 0.007), D-dimer≥3.35 mg/l (OR 8.49, 95% CI: 4.13-17.84,P<0.001), larger infarct volume (aOR 1.02, 95% CI: 1.00-1.03, P = 0.014), and higher CRUB-65 score (aOR 6.43, 95% CI: 3.10-13.34, P<0.001) were associated with increased risk of 3-month mortality. CONCLUSIONS: AF-related AIS patients with concurrent high D-dimer and pneumonia increased risk of 3-month mortality and death/severe disability, plasma D-dimer may have predictive value in outcome after AF-related AIS with pneumonia.

10.
Qual Life Res ; 2021 Mar 06.
Artigo em Inglês | MEDLINE | ID: mdl-33677773

RESUMO

PURPOSE: The purpose of this study was to analyse the trajectories of depression in urban and rural areas, and to analyse the relationship among multimorbidity, disability and other variables and trajectories. METHODS: Data from the China Health and Retirement Longitudinal Study were used. A latent class growth model was used to characterise the trajectories of urban and rural depression symptoms. Chi-square test was used to test the differences in respondents' characteristics among depression trajectories groups within urban and rural areas. The relationships among multimorbidity, disability and depression symptom trajectories were analysed via multinomial logistic regression. RESULTS: Urban and rural depression trajectories were divided into three categories. Respondents in urban areas were divided into rising, remaining-low and declining group, and those in rural areas were divided into rising, remaining-low and remaining-high group. The depression scores of respondents with multimorbidity were more likely to rise, and this result was similar for the disabled respondents. Respondents who need help on activities of daily living and instrumental activities of daily living in urban areas were more likely to decline in depression scores. In rural areas, however, the values were consistently high. In urban and rural areas, the relationships among marital status, education and age and depression trajectories were different. CONCLUSIONS: The depression trajectories are different in urban and rural China. Improving the quality of medical services, promoting the distribution of rural social resources and implementing more recreational activities could be beneficial for the promotion of mental health in rural areas.

11.
Med Oncol ; 38(5): 49, 2021 Mar 27.
Artigo em Inglês | MEDLINE | ID: mdl-33772655

RESUMO

Increasing evidence demonstrated that alternative splicing (AS) plays a vital role in tumorigenesis and clinical outcome of patient. However, systematical analysis of AS in lung squamous cell carcinoma (LUSC) is lacking and greatly necessary. Thus, this study was to systematically estimate the function of AS events served as prognostic indicators in LUSC. Among 31,345 mRNA AS events in 9633 genes, we detected 1996 AS in 1409 genes which have significant connection with overall survival (OS) of LUSC patients. Then, prognostic model based on seven types of AS events was established and we further constructed a combined prognostic model. The Kaplan-Meier curve results suggested that seven types of AS signatures and the combined prognostic model could exhibit robust performance in predicting prognosis. Patients in the high-risk group had significantly shorter OS than those in the low-risk group. The ROC showed all prognostic models had high accuracy and powerful predictive performance with different AUC ranging from 0.837 to 0.978. Moreover, the combined prognostic model had highest performance in risk stratification and predictive accuracy than single prognostic models and had higher accuracy than other mRNA model. Finally, a significant correlation network between survival-related AS genes and prognostic splicing factors (SFs) was established. In conclusion, our study provided several potential prognostic AS models and constructed splicing network between AS and SFs in LUSC, which could be used as potential indicators and treatment targets for LUSC patients.

12.
Mech Ageing Dev ; 195: 111452, 2021 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-33556365

RESUMO

Alzheimer's disease (AD) is the most common cause of dementia globally. AD is a progressive neurodegenerative disorder, eventually manifesting as severe cognitive impairment. Adult hippocampal neurogenesis (AHN) occurs throughout adulthood and plays an important role in hippocampus-dependent learning and memory. The stages of AHN, predominantly comprising the proliferation, differentiation, survival, and maturation of newborn neurons, are affected to varying degrees in AD. However, the exact molecular mechanisms remain to be elucidated. Recent evidence suggests that the molecules involved in AD pathology contribute to the compromised AHN in AD. Notably, various interventions may have common signaling pathways that, once identified, could be harnessed to enhance adult neurogenesis. This in turn could putatively rescue cognitive deficits associated with impaired neurogenesis as observed in animal models of AD. In this manuscript, we review the current knowledge concerning AHN under normal physiological and AD pathological conditions and highlight the possible role of specific molecules in AHN alteration in AD. In addition, we summarize in vivo experiments with emphasis on the effect of the activation of certain key signalings on AHN in AD rodent models. We propose that these signaling targets and corresponding interventions should be considered when developing novel therapies for AD.

13.
J Sci Food Agric ; 2021 Feb 04.
Artigo em Inglês | MEDLINE | ID: mdl-33543494

RESUMO

BACKGROUND: Hyperuricemia (HUA) is a serious public health concern globally that needs to be solved. It is closely related to gout and other metabolic diseases. To develop a safe and effective dietary supplementation for alleviating HUA, we investigated the effects of whey protein hydrolysate (WPH) on HUA and associated renal dysfunction and explored their underlying mechanism. RESULTS: Potassium oxonate was used to induce HUA in model rats, who were then administered WPH for 21 days. The results showed that WPH significantly inhibited xanthine oxidase and adenosine deaminase activity in serum and liver, decreased uric acid (UA), creatinine, and blood urea nitrogen levels in serum, and increased the UA excretion in urine. In addition, WPH downregulated the expression of urate transporter 1 and upregulated the expression of organic anion transporter 1, adenosine triphosphate binding cassette subfamily G member 2, organic cation/carnitine transporters 1 and 2, and organic cation transporter 1 in kidneys. CONCLUSION: These findings demonstrated for the first time that WPH could alleviate HUA by inhibiting UA production and promoting UA excretion, and improve the renal dysfunction caused by HUA. Thus, WPH may be a potential functional ingredient for the prevention and treatment of HUA and associated renal dysfunction. © 2021 Society of Chemical Industry.

14.
Trends Cell Biol ; 31(4): 237-240, 2021 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-33593679

RESUMO

Recent innovations in immunotherapies have cured cancers but remain ineffective in pancreatic cancer, which exhibits intertwined dynamics of dedifferentiation of epithelium and reprogramming of immunosuppression. Emerging evidence reveals the biological mechanisms through which dedifferentiation recapitulates immune reprogramming, providing new insights into the therapeutic potential of controlling dedifferentiation for sensitization to immunotherapies.

15.
J Org Chem ; 2021 Feb 12.
Artigo em Inglês | MEDLINE | ID: mdl-33577735

RESUMO

In order to prepare bridging chiral p-tert-butylcalix[4]crown-5 with a mononitro bridge substituent in a 1,3-alternate conformation, a mononitration method of calix[4]arene bridging methylene has been first developed with tert-butyl nitrite as a nitration reagent. The effects of solvent, reaction temperature, reaction time, and nitration reagent dosage on bridge mononitration have been deeply explored to obtain an optimal nitration condition. The facile nitration presents a new key for calix[4]arene bridge derivatization. After further modification and diastereoisomeric resolution, a pair of bridging chiral p-tert-butylcalix[4]arenes with a monoamino bridge substituent were produced from the bridge-mono-nitrated calix[4]arene. Their preliminary catalysis results in the Henry reaction show good catalytic activities (up to 95% yield) and still low but obviously enhanced enantioselectivities (up to 22.3% ee from 7a, 6% ee from 1), which confirms that the structural transformation indeed improves asymmetric catalysis performances of bridging chiral calix[4]crown-5 amines in a 1,3-alternate conformation.

16.
J Orthop Res ; 2021 Feb 02.
Artigo em Inglês | MEDLINE | ID: mdl-33533088

RESUMO

Estrogen deficiency has been shown to negatively influence rotator cuff tendon healing. Therefore, the addition of an estrogen-like-compound (ELC) in a nonestrogen-deficient animal may improve the quality of a rotator cuff repair. The purpose of this study was to evaluate the effects of an ELC, diethylstilbestrol (DES), on tendon healing in a murine rotator cuff repair model. Thirty-three male wild-type mice (C57BL/6NJ) were randomly divided into three study groups. Group 1-unoperated mice with normal rotator cuff tendons. Groups 2 and 3 consisted of surgically repaired rotator cuff tendons; Group 2 (repair-only) was the standard repair group (no DES injected), whereas Group 3 (repair + DES) was the experimental repair group (injected with DES). Comparing the maximal thickness of calcified fibrocartilage to uncalcified fibrocartilage, the ratios for the control (intact tendon), repair-only, and repair + DES groups were 2:1, 0.9:1, and 1.7:1. RNA expression data demonstrated upregulation of chondrogenic, angiogenic, and tendon modulation genes in the repair- only group compared to the control (intact tendon) group (p < 0.04 for all), and that addition of DES further increased the osteogenic, angiogenic, and tendon modulation gene expression compared to the repair-only group (p < 0.02). Immunohistochemical analysis indicated that the addition of DES further increased osteogenic, angiogenic, and tendon maturation protein expression at the enthesis compared to standard repairs.

17.
J Colloid Interface Sci ; 590: 467-475, 2021 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-33561596

RESUMO

With the rapid development of electronic communications, coated fabrics with EMI shielding capability have attracted increasing attention due to their broad applications in military, civilian, and commercial fields. The coating structure plays a vital role in EMI shielding performance and the fundamental understanding of how the coating structure affects the EMI shielding performance of the coated fabric is urgently needed. In this work, the coating structure has been systematically modulated to study its effects on the shielding performance of the corresponding coated fabric for the rational design of the high-performance EMI shielding materials. Owing to the multiple reflections of the electromagnetic waves triggered by the graphene oxide (GO)/ polypyrrole (PPy) interfaces, the shielding effectiveness (SE) of the coated fabric reaches 39.1 dB by increasing the amount of interface in the coating. Furthermore, more GO/PPy interfaces in the coating results in stronger EMI shielding enhancement once the conductive network is built. This work provides a guideline for the judicious design of shields to achieve excellent EMI shielding performances and offers opportunities for new-generation portable and wearable EMI shielding products.

18.
Artigo em Inglês | MEDLINE | ID: mdl-33547614

RESUMO

Although exposure to antibiotics at a critical developmental time window has been implicated in mental health in observational and experimental studies, very limited bio-monitoring data are available for exposure to antibiotics associated with child mental disorders. The goal of our study was to examine the association between urinary exposure of children to antibiotics and mental health. The participants were 278 children from 256 eligible families in the urban-rural fringe of Fuyang city in China since June in 2017. A single-point urine sample was collected to measure the antibiotic concentrations to characterize the exposure levels. A total of 45 antibiotics from nine classes and their two metabolites were monitored through liquid chromatography electrospray tandem mass spectrometry. We used multivariable regressions to estimate the covariate-adjusted associations between urine-antibiotic concentrations and mental impairments, as assessed using the parent version of Strengths and Difficulties Questionnaire. Among the participants, ciprofloxacin was associated with an increased risk of mental disorders at both lower concentrations (OR = 4.06; 95% CI 1.69-9.78) and higher concentrations OR = 6.04; 95% CI 2.59-14.08). After categorizing the detected antibiotics, the positive associations were observed between abnormal score in total difficulties and higher levels exposure to fluoroquinolones (OR = 2.83, 95% CI 1.38-5.80) and antibiotics preferred for veterinary use (PVAs) (OR = 3.20; 95% CI 1.41-7.27), respectively. Our findings suggest that ciprofloxacin, fluoroquinolones and PVAs, probably from contaminated food or environment, may be associated with child mental disorders.

19.
Reprod Biol Endocrinol ; 19(1): 5, 2021 Jan 07.
Artigo em Inglês | MEDLINE | ID: mdl-33407572

RESUMO

BACKGROUND: The etiology between homocysteine and polycystic ovary syndrome (PCOS) is unclear. In humans, the level of homocysteine is mainly affected by two enzymes: methylene tetrahydrofolate reductase (MTHFR) and methionine synthase reductase (MTRR). While the activity of these two enzymes is mainly affected by three missense mutations, namely C677T (MTHFR), A1298C (MTHFR), and A66G (MTRR). This study aims to examine the association between the three missense mutations and PCOS and investigate whether the three missense mutations exerted their effect on PCOS by affecting the homocysteine level. METHODS: A case-control study was designed, comprising 150 people with PCOS and 300 controls. Logistic regression analysis was used to assess the association between the three missense mutations and PCOS. Linear regression analysis was used to assess the association between the three missense mutations and the homocysteine level. Mediation analysis was used to investigate whether the three missense mutations exerted their effect on PCOS by affecting the homocysteine level. RESULTS: Following adjustments and multiple rounds of testing, MTHFR A1298C was found to be significantly associated with PCOS in a dose-dependent manner (compared to AA, OR = 2.142 for AC & OR = 3.755 for CC; P < 0.001). MTRR A66G was nominally associated with PCOS. Mutations in MTHFR A1298C and MTRR A66G were significantly associated with the homocysteine level. Mediation analysis suggested the effect of MTHFR A1298C on PCOS was mediated by homocysteine. CONCLUSIONS: MTHFR A1298C and MTRR A66G were associated with PCOS, and MTHFR A1298C might affect the risk of PCOS by influencing the homocysteine level.

20.
Orphanet J Rare Dis ; 16(1): 7, 2021 Jan 06.
Artigo em Inglês | MEDLINE | ID: mdl-33407670

RESUMO

BACKGROUND: Spinal muscular atrophy (SMA) is an autosomal-recessive motor neuron disease leading to dysfunction of multiple organs. SMA can impair the quality of life (QoL) of patients and family. We aimed to evaluate the QoL of children with SMA and their caregivers and to identify the factors associated with QoL in a cross-sectional study conducted in China. METHODS: We recruited 101 children aged 0-17 years with SMA and their caregivers from a children's hospital in China. Twenty-six children had type I SMA, 56 type II and 19 type III. Each child's QoL was measured by the Pediatric Quality of Life Inventory 3.0 Neuromuscular Module (PedsQL NMM), which was completed by the child's caregivers. The caregiver's QoL was measured by the Pediatric Quality of Life Inventory Family Impact Module (PedsQL FIM). Information on sociodemographic characteristics, disease-specific characteristics, and treatments were collected using the proxy-reported questionnaire. Two-sample t tests and one-way ANOVA were used to compare differences in average scores of QoL across subgroups. RESULTS: Children with type III SMA had a higher average Total score of PedsQL NMM and higher average scores in domains Neuromuscular disease and Family resources than children with type I or type II SMA (p < 0.001). Caregivers of children with type III SMA reported higher average scores in the domains of Physical, Emotional, Social, and Cognitive functioning of the PedsQL FIM than those of children with types I or II SMA (p < 0.05). In addition, disease-related characteristics (e.g. limited mobility, stable course of disease, skeleton deformity, and digestive system dysfunction) and respiratory support were associated with lower average scores of PedsQL NMM and PedsQL FIM (p < 0.05). Exercise training, multidisciplinary team management and use of the medication Nusinersen were each associated with higher average scores in both PedsQL NMM and FIM (p < 0.05). CONCLUSION: Our study has demonstrated factors that may impair or improve QoL of children patients with SMA and their parents. Particularly, QoL was relatively poor in children with type I and type II SMA as well as in their caregivers compared to those with type III SMA. We strongly recommend that standard of care in a multidisciplinary team be strengthened to improve the QoL of SMA patients. Our study called for increased attention from clinical physicians on measuring QoL in their clinical practices in order to enhance the understanding of impacts of SMA and to make better decisions regarding treatment.

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