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1.
Nanoscale ; 13(22): 9989-10001, 2021 Jun 14.
Artigo em Inglês | MEDLINE | ID: mdl-34076013

RESUMO

Photodynamic therapy (PDT) is frequently used in cancer treatment in clinical settings. However, its applications in stroma-rich solid tumors, e.g., triple negative breast cancer, are limited by abnormal mechanical microenvironments. Solid stress accumulated in stroma-rich solid tumors compresses tumor blood vessels, hampers the delivery of photosensitizers (PSs) in tumor tissues, and poses a major challenge for potent PDT. Here, we report a novel combination strategy to augment PDT based cancer therapy by combining hydroxyethyl starch-chlorin e6 conjugate self-assembled nanoparticles (HES-Ce6 NPs) with the transforming growth factor-ß (TGFß) inhibitor LY2157299 (LY). HES-Ce6 conjugates, as synthesized by one step esterification reaction, could self-assemble into uniform HES-Ce6 NPs, which exhibited enhanced photostability and generated more reactive oxygen species (ROS) under 660 nm laser irradiation than free Ce6. Prior to PDT, intragastric administration of LY decreased collagen deposition, alleviated solid stress, and decompressed tumor blood vessels. As a result, the reconstructed tumor mechanical microenvironment promoted accumulation and penetration of HES-Ce6 NPs into tumor tissues, contributing to augmented antitumor efficacy of HES-Ce6 NP mediated PDT. Modulating tumor mechanical microenvironments using TGFß blockade to enhance the delivery of PSs in tumors with excessive extracellular matrix represents an efficient strategy for treating stroma-rich solid tumors.


Assuntos
Nanopartículas , Neoplasias , Fotoquimioterapia , Porfirinas , Linhagem Celular Tumoral , Humanos , Fármacos Fotossensibilizantes/farmacologia , Porfirinas/farmacologia , Fator de Crescimento Transformador beta , Fatores de Crescimento Transformadores , Microambiente Tumoral
2.
Adv Sci (Weinh) ; : e2100233, 2021 Jun 03.
Artigo em Inglês | MEDLINE | ID: mdl-34085419

RESUMO

Aberrant mechanical properties and immunosuppression are the two key factors that limit the antitumor efficacy of T cell immune checkpoint blockade inhibitors, e.g., programmed cell death-1 antibody (PD-1 Ab), against solid tumors in the clinic. This study leverages hyperbaric oxygen (HBO) for the first time to address these two issues and reports the PD-1-Ab-mediated immune responses against various stroma-rich solid malignancies. The results demonstrate that HBO promoted PD-1 Ab delivery and T cells infiltration into tumor parenchyma by depleting the extracellular matrix's main components, such as collagen and fibronectin. Furthermore, HBO disrupts hypoxia-mediated immunosuppression and helps PD-1 Ab trigger robust cytotoxic T lymphocytes and long-lasting immunological memory to inhibit tumor relapses. Such enhanced immune responses are effective in solid tumors from rodents and the cancer cells from hepatocellular carcinoma patients. The results illustrate that HBO bolsters antitumor efficacy of PD-1 Ab, and the HBO-PD-1 Ab combination is a promising stroma-rich solid tumors' treatment in the clinic.

4.
J Psychiatr Res ; 140: 282-288, 2021 Jun 04.
Artigo em Inglês | MEDLINE | ID: mdl-34126421

RESUMO

OBJECTIVE: Studies have found that there may be qualitative changes in brain structure and function in adolescents with early-onset schizophrenia (EOS) and prodromal schizophrenia (PDS). However, the abnormal brain structure and function of adolescents with EOS and PDS have received little attention, and their underlying neural mechanisms are still unknown. METHODS: In this study, structural and resting-state functional magnetic resonance imaging (fMRI) were used to compare the subcortical volume and functional connectivity (FC) among EOS, PDS, and a control group. The Positive and Negative Symptom Scale (PNASS) questionnaire was used for clinical evaluation. Structural MRI was used to calculate cortical-based morphological volume and subcortical volume, and resting-state fMRI was used to analyze seed-based FC. RESULTS: Structural MRI analyses showed that the gray matter volume of the hippocampus in EOS was significantly smaller than that in the control group, and the gray matter volume of the hippocampus, amygdala, and caudate nucleus in PDS was significantly smaller than that in the control group. Additionally, correlation analysis showed that the gray matter volume of the hippocampus was significantly negatively correlated with the negative symptom score of PANSS in EOS. When the hippocampus was used as the seed, fMRI analysis found that the FC between the hippocampus and the posterior cingulate gyrus and precuneus in EOS was significantly weaker than that in the control group. CONCLUSION: Our results indicate that the brain structure and function are abnormal in EOS and PDS, with abnormalities mainly concentrated in the limbic system, including the hippocampus, amygdala, caudate nucleus, cingulate gyrus, and precuneus. These findings provide a new direction for early intervention and improvement of the prognosis of schizophrenic patients.

5.
Neuroscience ; 467: 134-141, 2021 May 24.
Artigo em Inglês | MEDLINE | ID: mdl-34038771

RESUMO

The purpose of this study is to probe into the influence mechanism of parental emotional warmth (PEW) on extraversion for children and adolescents, as well as the moderating and mediating role of brain functional activity. Thirty-two children and adolescents underwent functional magnetic resonance imaging (fMRI) scans and completed Egna Minnen av Barndoms Uppfostran (EMBU) and Eysenck Personality Questionnaire (EPQ). Small-worldness (SW) of brain networks, fractional amplitude of low-frequency fluctuations (fALFF), and region-of-interest to region-of-interest (ROI-ROI) functional connectivity were calculated to study intrinsic neuronal activity. We found that PEW had a positive direct effect on extraversion, and all participants in the current study showed an efficient small-world structure. The positive association between PEW and extraversion was mediated by SW. Furthermore, the fALFF and extraversion were significantly and negatively correlated in the right precuneus and dorsolateral superior frontal gyrus. The mediating effect of SW was moderated by the functional connectivity between the right precuneus and the right dorsolateral superior frontal gyrus. The indirect effect was significant with lower level of the functional connectivity between the right precuneus and the right dorsolateral superior frontal gyrus. These findings indicate that SW of brain networks may be a key factor that accounts for the positive association between PEW and extraversion in children and adolescents and the level of the functional connectivity between the right precuneus and the right dorsolateral superior frontal gyrus could moderate the relationship.

6.
Zhongguo Zhong Yao Za Zhi ; 46(7): 1727-1737, 2021 Apr.
Artigo em Chinês | MEDLINE | ID: mdl-33982476

RESUMO

Methotrexate(MTX) is a commonly used antimetabolite, which can be used in the treatment of a variety of diseases. However, hepatotoxicity in the use of MTX severely limits its clinical use. Therefore, how to prevent and treat hepatotoxicity of MTX has become an urgent clinical problem. This paper summarizes and analyzes relevant literatures on the prevention and treatment of hepa-totoxicity caused by MTX with traditional Chinese medicines and natural medicines in recent years. MTX-induced hepatotoxicity mechanisms include folate pathway, oxidative stress damage and adenosine pathway, of which oxidative stress theory is the main research direction. A total of 14 kinds of traditional Chinese medicine and natural medicine extracts including white peony root, and 21 kinds of natural monomer compounds, including berberine, play an anti-MTX-induced hepatotoxic effect by resisting oxidative stress, inhibiting inflammation and regulating signal pathways. According to current studies on the prevention and treatment of hepatotoxicity induced by MTX with traditional Chinese medicines and natural medicines, there are insufficiencies, such as partial and superficial mechanism studies, inadequate combination of experimental research and clinical practice, non-standard experimental design and lack of application of advanced technologies and methods. This paper systematically reviewed the effects and mechanisms of traditional Chinese medicines and natural medicines against hepatotoxicity induced by MTX and defined current studies and deficiencies, in the expectation of proposing new study strategies and directions and providing scientific basis for rational clinical use of MTX and development of new drugs against MTX hepatotoxicity.


Assuntos
Doença Hepática Induzida por Substâncias e Drogas , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos , Doença Hepática Induzida por Substâncias e Drogas/tratamento farmacológico , Doença Hepática Induzida por Substâncias e Drogas/etiologia , Doença Hepática Induzida por Substâncias e Drogas/prevenção & controle , Humanos , Fígado/metabolismo , Medicina Tradicional Chinesa , Metotrexato/toxicidade , Estresse Oxidativo
7.
Brain Res Bull ; 173: 162-173, 2021 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-34044033

RESUMO

AIMS: Cholesteryl ester(CE), generated from the mitochondria associated membrane (MAM), is involved in the pathogenesis of Alzheimer's Disease (AD). In theory, the different neuroprotective effects of progesterone in AD are all linked to MAM, yet the effect on cholesterol esterification has not been reported. Therefore, this study was aimed to investigate the regulation of progesterone on intracerebral CE in AD models and the underlying mechanism. METHODS: APP/PS1 mice and AD cell model induced by Aß 25-35 were selected as the research objects. APP/PS1 mice were daily administrated intragastrically with progesterone and The Morris Water Maze test was performed to detect the learning and memory abilities. Intracellular cholesterol was measured by Cholesterol/Cholesteryl Ester Quantitation Assay. The structure of MAMs were observed with transmission electron microscopy. The expression of acyl-CoA: cholesterol acyltransferase 1 (ACAT1), ERK1/2 and p-ERK1/2 were detected with western blotting, immunohistochemistry or immunofluorescence. RESULTS: Progesterone suppressed the accumulation of intracellular CE, shortened the length of abnormally prolonged MAM in cortex of APP/PS1 mice. Progesterone decreased the expression of ACAT1, which could be blocked by progesterone receptor membrane component 1 (PGRMC1) inhibitor AG205. The ERK1/2 pathway maybe involved in the progesterone mediated regulation of ACAT1 in AD models, rather than the PI3K/Akt and the P38 MEPK pathways. SIGNIFICANCE: The results supported a line of evidence that progesterone regulates CE level and the structure of MAM in neurons of AD models, providing a promising treatment against AD on the dysfunction of cholesterol metabolism.

8.
Biomed Res Int ; 2021: 6637235, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33997033

RESUMO

Objectives: Systemic vasculitis includes a group of disorders characterized by inflammation of the vessel wall, involving multiple systems, and can cause malignant hypertension. CD163 is a specific marker of anti-inflammatory macrophages. This study is aimed at evaluating the CD163 levels in relation to systemic vasculitis and renal involvements. Methods: Urinary CD163 levels were retrospectively measured by enzyme-linked immunosorbent assay (ELISA) in 51 patients with systemic vasculitis, 42 essential hypertensions, and 36 healthy volunteers. The associations between urinary CD163 levels and clinical indicators were analyzed. Results: Urinary CD163 levels were significantly higher in patients with systemic vasculitis [68.20 (38.25~158.78) (pg/ml)] compared to essential hypertension [43.86 (23.30-60.71) (pg/ml)] (p = 0.003) and the healthy volunteers [30.76 (9.30-54.16) (pg/ml)] (p < 0.001). Furthermore, systemic vasculitis patients with renal involvement had significantly higher urinary CD163 levels relative to patients without renal involvement [86.95 (47.61 and 192.38) pg/ml] vs. [41.99 (17.70 and 71.95) pg/ml, p = 0.005]. After control factors age, sex, and BMI, urinary CD163 levels in systemic vasculitis patients were positively correlated with serum creatinine, blood urea nitrogen, and ß-2 microglobulin (r = 0.45, 0.48, and 0.46; p = 0.001, 0.001, and 0.002, respectively). In addition, we found the level of urinary CD163 in granulomatous vasculitis (including TA, GPA, and EGPA) was significantly higher than that in necrotizing vasculitis (including PAN) [86.95 (41.99 and 184.82) pg/ml] vs. [45.73 (21.43 and 74.43) pg/ml, p = 0.016]. Conclusion: Urinary CD163 levels were significantly higher in patients with systemic vasculitis, especially in patients with renal involvement. Thus, urinary CD163 has the potential to be a biomarker for systemic vasculitis with renal involvement.


Assuntos
Antígenos CD/urina , Antígenos de Diferenciação Mielomonocítica/urina , Nefropatias/urina , Vasculite Sistêmica/urina , Adulto , Idoso , Idoso de 80 Anos ou mais , Biomarcadores/urina , Estudos Transversais , Ensaio de Imunoadsorção Enzimática , Feminino , Humanos , Nefropatias/complicações , Masculino , Pessoa de Meia-Idade , Receptores de Superfície Celular , Estudos Retrospectivos , Vasculite Sistêmica/complicações , Adulto Jovem
9.
Biomed Res Int ; 2021: 6657476, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33954193

RESUMO

Objective: It is aimed at investigating the mechanism of palmitic acid (PA) on myocardial contractility in hypertensive rats and its relationship with myocardial neural nitric oxide synthase (nNOS) protein. Methods: The rats were randomly divided into sham operation group and hypertensive group, with thirty rats in each group, to prepare angiotensin II-induced hypertensive model rats. The blood pressure of rats was measured by the multianimal multichannel tail cuff noninvasive blood pressure system of Kent Coda, USA. The Ionoptix single-cell contraction detection system was used to detect myocardial cells. ATP level of left ventricular cardiomyocytes was determined by luminescence method, and protein was measured by Western blot. Results: Compared with the sham group, systolic blood pressure and diastolic blood pressure were increased in the hypertensive group over 4 weeks; PA increased the contractility of left ventricular cardiomyocytes in normal rats, but not in hypertensive rats, and PA increased the intracellular ATP level of rats in the sham group but not in the hypertension group. In the hypertension group, the expression of nNOS in the cardiomyocytes was significantly increased, and specific nNOS inhibitor S-methyl-L-thiocitrulline (SMTC) was found to restore the positive inotropic effect of PA in the myocardium of the hypertension group. PA was supplemented after using CPT-1 inhibitor etomoxir (ETO); it was found that ETO inhibited the positive inotropic effect of PA on left ventricular cardiomyocytes in the sham group, and PA was supplemented after using SMTC and ETO, it was found that SMTC + ETO could inhibit the positive inotropic effect of PA on left ventricular cardiomyocytes in myocardium of hypertensive rats. Conclusion: PA could increase the contractility of healthy cardiomyocytes, but had no obvious positive effect on the cardiomyocytes of hypertensive rats, PA enhanced the contractility of cardiomyocytes by increasing ATP level in them, and the inhibitory effect of PA on myocardial contractility in hypertensive rats may be related to the increased nNOS and CPT-1 in cardiomyocytes.


Assuntos
Contração Muscular/efeitos dos fármacos , Miócitos Cardíacos/enzimologia , Óxido Nítrico Sintase Tipo I/metabolismo , Ácido Palmítico/farmacologia , Trifosfato de Adenosina/metabolismo , Animais , Pressão Sanguínea/efeitos dos fármacos , Carnitina O-Palmitoiltransferase/antagonistas & inibidores , Carnitina O-Palmitoiltransferase/metabolismo , Compostos de Epóxi/farmacologia , Hipertensão/fisiopatologia , Masculino , Miócitos Cardíacos/efeitos dos fármacos , Miócitos Cardíacos/metabolismo , Ratos Endogâmicos SHR , Ratos Sprague-Dawley
10.
Acta Otolaryngol ; 141(6): 551-556, 2021 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-33819124

RESUMO

BACKGROUND: No cochlear otosclerosis in infants with congenital bilateral SNHL has been reported. AIMS/OBJECTIVES: We report an infant male with bilateral cochlear otosclerosis, suggesting that cochlear otosclerosis may be a congenital disease and to further analyze the etiology of and genetic expression in congenital bilateral cochlear otosclerosis. We also describe the clinical characteristics and experience of patients with bilateral cochlear otosclerosis treated with cochlear implants (CIs). MATERIALS AND METHODS: Seven patients, including an infant, who were diagnosed with cochlear otosclerosis underwent CI surgery. Their medical records, audiological and radiological results, surgical procedures, and CI outcomes were collected and reviewed. RESULTS: The median age at hearing loss was 38 years, ranging from 0 to 47 years. The child had bilateral hearing loss at birth and received a CI at 1 year of age. He also had growth retardation and was diagnosed with 3q+/3p- syndrome. All patients (8 ears) had better postoperative auditory performance than that preoperatively. CONCLUSIONS AND SIGNIFICANCE: Although cochlear otosclerosis often starts at middle age and progresses slowly, it may be a congenital disease that is related to chromosome abnormality. This disease presents with SNHL or MHL, and treatment with a CI is beneficial.

11.
J Matern Fetal Neonatal Med ; : 1-9, 2021 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-33792471

RESUMO

OBJECTIVES: To evaluate the performance of noninvasive prenatal screening (NIPS) for the fetal common aneuploidy screening in twin pregnancies. METHODS: The data of 5469 women with twin pregnancies were collected in this retrospective observational study between January 2017 and December 2018. Patients underwent NIPS as first-line screening or after standard serum screening for fetal aneuploidy. The performance of NIPS was examined, and a regression analysis was performed to investigate testing failure in cases of low fetal fraction. RESULTS: In this study, 2231 (40.8%) patients opted for NIPS as the primary prenatal screening test, and 3238 (59.2%) opted for serum screening, including 440 patients who opted for NIPS after serum screening. Among the 2671 pregnancies with available NIPS outcomes, 11 cases of aneuploidy were identified, seven of trisomy 21 and four of sex chromosome aneuploidy (SCA). The sensitivity and specificity for trisomy 21 were 100% (95% CI, 56.1-100.0%) and 100% (95% CI, 99.8-100.0%), respectively. The positive predictive value (PPV) for SCA was 40.0% (95% CI, 13.7-72.6%). No false negatives were found, with a negative predictive value (NPV) of 100% (95% CI, 99.8-100.0%) in total. In 32 pregnancies who failed NIPS test without available NIPS outcomes due to low fetal fraction, the regression analysis demonstrated that increasing BMI and assisted reproductive technology treatment were significant independent predictors. CONCLUSIONS: NIPS is a high-performing routine primary prenatal screening test in twin pregnancies, with a high PPV and low false positive rate for detecting trisomy 21. It is also useful to identify common sex chromosome aneuploidies in twin pregnancies, with similar performance to that reported in singleton pregnancy.

12.
Inquiry ; 58: 469580211007221, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33834860

RESUMO

This research is primarily focused on the issues of customer loyalty in the healthcare industry, particularly from the perspective of public hospitals in China. The research developed a theoretical model to test the relationship between patient satisfaction (PS), patient trust (PT), and patient loyalty (PL). The empirical data were collected from 1696 patients through the survey questionnaires from the public hospitals in Henan province. This research is an explanatory study, and adopts quantitative method. The measurement scales used in the survey were assessed and refined and the data analysis was performed using AMOS 19.0 to test the theoretical model and hypotheses developed. In addition, an exploratory factor analysis was used to identify the dimensions of PS, PT, and PL. Their reliability and validity were established through confirmatory factor analysis, and the structural equation modeling (SEM) was used in the related hypotheses. The findings indicate that PT is an important antecedent of PL, and PS has no direct relationship with PL. It is worth noting that PS can lead to PL with PT as the mediating variable. The survey results will help public hospital managers to formulate effective strategies and provide a basis for studying PL. The research will prompt hospital managers to pay attention to the factors which contribute to PS, PT, and PL, and maintain the loyalty of patients to medical institutions. This study is one of the few studies on the relationship between PS, PT, and PL in Chinese public hospitals, and it also explores the direct and indirect effects of PT on PL. The results have practical implications for the Chinese healthcare industry.

13.
Mikrochim Acta ; 188(5): 168, 2021 Apr 21.
Artigo em Inglês | MEDLINE | ID: mdl-33884514

RESUMO

Metal-organic frameworks (MOFs) have captured substantial attention of an increasing number of scientists working in sensing analysis fields, due to their large surface area, high porosity, and tunable structure. Recently, MOFs as attractive fluorescence quenchers have been extensively investigated. Given their high quenching efficiency toward the fluorescence intensity of dyes-labeled specific biological recognition molecules, such as nucleic acids, MOFs have been widely developed to switch fluorescence biosensors with low background fluorescence signal. These strategies not only lead to specificity, simplicity, and low cost of biosensors, but also possess advantages such as ultrasensitive, rapid, and multiple detection of switch fluorescence methods. At present, researches of the analysis of switch fluorescence biosensors based on MOFs and nucleic acids mainly focus on sensing of different types of in vitro and intracellular analytes, indicating their increasing potential. In this review, we briefly introduce the principle of switch fluorescence biosensor and the mechanism of fluorescence quenching of MOFs, and mainly discuss and summarize the state-of-the-art advances of MOFs and nucleic acids-based switch fluorescence biosensors over the years 2013 to 2020. Most of them have been proposed to the in vitro detection of different types of analytes, showing their wide scope and applicability, such as deoxyribonucleic acid (DNAs), ribonucleic acid (RNAs), proteins, enzymes, antibiotics, and heavy metal ions. Besides, some of them have also been applied to the bioimaging of intracellular analytes, emerging their potential for biomedical applications, for example, cellular adenosine triphosphate (ATP) and subcellular glutathione (GSH). Finally, the remaining challenges in this sensing field and prospects for future research trends are addressed. Graphical abstract.

14.
J Ethnopharmacol ; 275: 114129, 2021 Jul 15.
Artigo em Inglês | MEDLINE | ID: mdl-33878416

RESUMO

ETHNOPHARMACOLOGICAL RELEVANCE: Curculigo orchioides Gaertn is used for the treatment of impotence, atrophic debility of bones (osteoporosis), limb limpness, and arthritis of the lumbar and knee joints in traditional Chinese medicine and Ayurvedic medical system. Curculigoside (Cur) from Curculigo orchioides Gaertn has been shown to have regulatory effects on bone metabolism via anti-oxidative activities in rats and osteoblasts. However, little is known about the molecular pharmacological activity of Cur in osteoclastic bone resorption. AIM: The aim of this work is to investigate the inhibitory effect of Cur against osteoclasts (OCs) under the oxidative stress status, and explore the possible underlying mechanism. MATERIALS AND METHODS: OCs were induced from RAW264.7 cells using RANKL and H2O2. The number of OCs was measured by tartrate-resistant acid phosphatase (TRAP) staining. F-Actin and nuclear translocation of P65 and Nrf2 were stained with immunofluorescence assay and observed under a laser confocal microscope. The biochemical parameters of OCs were detected with an ELISA kit. The expression of Nrf2 and NF-κB pathway-related proteins was analyzed by Western Blot. RESULTS: Cur inhibited the TRAP activity, release of degrading products from bone slices and the expression of NFATc1, c-Fos, Cathepsin K (Ctsk) and matrix metallopeptidase 9 (MMP9) of OCs induced with RANKL and H2O2. In addition, Cur suppressed the ROS level and NADPH oxidase 1(NOX1) and NADPH oxidase 4 (NOX4) activities of OCS. More importantly, Cur enhanced the expression and nucleus translocation of Nrf2 and activities of its regulatory cytoprotective enzymes, and reduced the NF-κB expression and phosphorylation and nucleus translocation of p65 in OCs. Furthermore, the Nrf2 inhibitor ML385 and NF-κB inhibitor Bay11-7082 counteracted the effect of Cur in OCs. CONCLUSION: Cur mitigated oxidative stress and osteoclastogenesis by activating Nrf2 and inhibiting the NF-κB pathway, suggesting that Cur may prove to be a promising candidate for the treatment of osteoporosis. Our findings may also help partially explain the rationale behind the traditional use of Curculigo orchioides Gaertn.

15.
Epilepsy Behav ; 118: 107926, 2021 05.
Artigo em Inglês | MEDLINE | ID: mdl-33862535

RESUMO

BACKGROUND: Epilepsy, one of the most common and serious chronic neurological diseases, is accompanied by a series of complex psychosocial problems. A number of qualitative studies have investigated the stigma experiences among patients with epilepsy (PWE). However, the findings are different and complementary to a certain degree. We conducted a systematic review to investigate and synthesize existing qualitative research findings to fully identify stigma experienced by PWE. The aim was to develop anti-stigma interventions and reduce any adverse sequelae. OBJECTIVE: To synthesize qualitative evidence on the stigma experiences of PWE. METHODS: This was a systematic review and qualitative evidence synthesis guided by the Joanna Briggs Methodology. Systematic literature search for primary studies was conducted in PubMed, PsychINFO, EMBASE, and Web of Science databases until December 2019. Findings from the included qualitative studies were extracted, assessed for quality, and aggregated using meta-synthesis. RESULTS: Twenty-six studies were included in the review. Four distinct synthesized findings were identified from the original researches: 'stigma experienced in daily life'; 'stigma perceived from others'; 'psychological reactions to stigma'; and 'strategies to address stigma'. CONCLUSION: The present meta-synthesis thoroughly investigated the stigma experienced by PWE. The findings suggest that appropriate multi-level interventions targeting the general public, health professionals, caregivers, and patients themselves are warranted to reduce the harmful impacts of stigma.


Assuntos
Epilepsia , Estigma Social , Cuidadores , Pessoal de Saúde , Humanos , Pesquisa Qualitativa
16.
Allergy ; 2021 Apr 30.
Artigo em Inglês | MEDLINE | ID: mdl-33930199

RESUMO

BACKGROUND: Staphylococcus aureus is a pathogen of major concern in both acute infections and chronic conditions such as chronic rhinosinusitis (CRS). Bacteriophage (phage) therapy has recently regained interest for its potential to treat infections caused by antibiotic resistant strains including Methicillin Resistant Staphylococcus aureus (MRSA). However, bacteria can adapt and become resistant to phages. The aim of this study is to determine the potential for antibiotics to overcome phage resistance. METHODS: The susceptibility of S. aureus clinical isolates (CIs) to phages J-Sa36, Sa83 and Sa87 alone or in combination with protein synthesis inhibitor (PSI) antibiotics clindamycin, azithromycin and erythromycin was assessed using plaque spot assays, minimum inhibitory concentration (MIC) assays, double layer spot assays and resazurin assays. The safety and efficacy of subinhibitory PSI antibiotics in combination with phage was tested in a Sprague Dawley rat model of sinusitis infected with a phage resistant S. aureus CI. RESULTS: All three antibiotics at subinhibitory concentrations showed synergy when combined with all 3 phages against S. aureus CIs in planktonic and biofilm form and could sensitize phage-resistant S. aureus to promote phage infection. The combination of topical subinhibitory clindamycin or azithromycin and phage was safe and could eradicate S. aureus sinonasal biofilms in vivo. CONCLUSION: Subinhibitory concentrations of PSI antibiotics could sensitize phage-resistant S. aureus and MRSA strains to phages in vitro and in vivo. This data supports the potential use of phage-PSI antibiotic combination therapies, in particular for difficult-to-treat infections with phage-resistant S. aureus and MRSA strains.

17.
Pathogens ; 10(2)2021 Feb 14.
Artigo em Inglês | MEDLINE | ID: mdl-33672855

RESUMO

Corynebacterium accolens is the predominant species of the healthy human nasal microbiota, and its relative abundance is decreased in the context of chronic rhinosinusitis (CRS). This study aimed to evaluate the antimicrobial potential of C. accolens isolated from a healthy human nasal cavity against planktonic and biofilm growth of Staphylococcus aureus (S. aureus) and methicillin-resistant S. aureus (MRSA) clinical isolates (CIs) from CRS patients. Nasal swabs from twenty non-CRS control subjects were screened for the presence of C. accolens using microbiological and molecular techniques. C. accolens CIs and their culture supernatants were tested for their antimicrobial activity against eight S. aureus and eight MRSA 4CIs and S. aureus ATCC25923. The anti-biofilm potential of C. accolens cell-free culture supernatants (CFCSs) on S. aureus biofilms was also assessed. Of the 20 nasal swabs, 10 C. accolens CIs were identified and confirmed with rpoB gene sequencing. All isolates showed variable antimicrobial activity against eight out of 8 S. aureus and seven out of eight MRSA CIs. Culture supernatants from all C. accolens CIs exhibited a significant dose-dependent antibacterial activity (p < 0.05) against five out of five representative S. aureus and MRSA CIs. This inhibition was abolished after proteinase K treatment. C. accolens supernatants induced a significant reduction in metabolic activity and biofilm biomass of S. aureus and MRSA CIs compared to untreated growth control (p < 0.05). C. accolens exhibited antimicrobial activity against S. aureus and MRSA CIs in both planktonic and biofilm forms and holds promise for the development of innovative probiotic therapies to promote sinus health.

18.
J BUON ; 26(1): 294, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33721479

RESUMO

The Editors of JBUON issue an Expression of Concern to '4-Terpineol exhibits potent in vitro and in vivo anticancer effects in Hep-G2 hepatocellular carcinoma cells by suppressing cell migration and inducing apoptosis and sub-G1 cell cycle arrest', by Sha Liu, Yong Zhao, Hai-Feng Cui, Chun-Yu Cao, Yi-Bing Zhang, JBUON 2016;21(5):1195-1202; PMID:27837623. Following the publication of the above article, readers drew to our attention that part of the data was possibly unreliable. We sent emails to the authors with a request to provide the raw data to prove the originality, but received no reply. Therefore, as we continue to work through the issues raised, we advise readers to interpret the information presented in the article with due caution. We thank the readers for bringing this matter to our attention. We apologize for any inconvenience it may cause.

19.
J BUON ; 26(1): 297, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33721482

RESUMO

The Editors of JBUON issue an Expression of Concern to 'Anticancer activity of safranal against colon carcinoma is due to induction of apoptosis and G2/M cell cycle arrest mediated by suppression of mTOR/PI3K/Akt pathway', by Yibing Zhang, Yong Zhao, Jianyou Guo, Haifeng Cui, Sha Liu, JBUON 2018;23(3):574-578; PMID:30003721. Following the publication of the above article, readers drew to our attention that part of the data was possibly unreliable. We sent emails to the authors with a request to provide the raw data to prove the originality, but received no reply. Therefore, as we continue to work through the issues raised, we advise readers to interpret the information presented in the article with due caution. We thank the readers for bringing this matter to our attention. We apologize for any inconvenience it may cause.

20.
J Int Med Res ; 49(3): 300060521996929, 2021 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-33787386

RESUMO

OBJECTIVE: To investigate the metastatic mechanism of muscle invasive bladder cancer (MIBC), which accounts for approximately 30% of all bladder cancer cases, and is a considerable medical problem with high metastatic and mortality rates. METHODS: The mRNA levels of patients with metastatic MIBC and nonmetastatic MIBC from The Cancer Genome Atlas dataset were compared. An integrated bioinformatics analysis was performed of the differentially expressed genes (DEGs), and analyses of Gene Ontology, Kyoto Encyclopaedia of Genes and Genomes pathway, protein-protein interaction, and survival were performed to investigate differences between metastatic and nonmetastatic MIBC. RESULTS: Data from 264 patients were included (131 with, and 133 without, metastasis). A total of 385 significantly DEGs were identified, including 209 upregulated genes and 176 downregulated genes. Based on results using the STRING database and the MCODE plugin of Cytoscape software, two clusters were obtained. Moreover, two genes were identified that may be valuable for prognostic analysis: Keratin 38, type I (KRT38) and Histone cluster 1, H3f (HIST1H3F). CONCLUSION: The KRT38 and HIST1H3F genes may be important in metastasis of MIBC.


Assuntos
Neoplasias da Bexiga Urinária , Perfilação da Expressão Gênica , Regulação Neoplásica da Expressão Gênica , Redes Reguladoras de Genes , Humanos , Mapas de Interação de Proteínas , RNA Mensageiro/genética , Neoplasias da Bexiga Urinária/genética
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