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1.
Acta Pharm Sin B ; 2021 Sep 20.
Artigo em Inglês | MEDLINE | ID: mdl-34567957

RESUMO

COVID-19 pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has spread across the globe, posing an enormous threat to public health and safety. Traditional Chinese medicine (TCM), in combination with Western medicine (WM), has made important and lasting contributions in the battle against COVID-19. In this review, updated clinical effects and potential mechanisms of TCM, presented in newly recognized three distinct phases of the disease, are summarized and discussed. By integrating the available clinical and preclinical evidence, the efficacies and underlying mechanisms of TCM on COVID-19, including the highly recommended three Chinese patent medicines and three Chinese medicine formulas, are described in a panorama. We hope that this comprehensive review not only provides a reference for health care professionals and the public to recognize the significant contributions of TCM for COVID-19, but also serves as an evidence-based in-depth summary and analysis to facilitate understanding the true scientific value of TCM.

2.
Medicine (Baltimore) ; 100(36): e27178, 2021 Sep 10.
Artigo em Inglês | MEDLINE | ID: mdl-34516515

RESUMO

ABSTRACT: Small nucleolar RNA host gene 16 (SNHG16) has recently been reported as a potential biomarker in various cancers. However, the prognostic value of SNHG16 in hepatocellular carcinoma (HCC) has not been investigated yet. Therefore, the purpose of this study was to reveal the association between SNHG16 expression and clinicopathological characteristics of HCC.Standards-compliant literature was retrieved from multiple public databases, and data on overall survival, disease-free survival, and clinicopathological characteristics related to SNGH16 were extracted and meta-analysis was performed. Additionally, the Cancer Genome Atlas data were analyzed through the gene expression profiling interactive analysis database to verify previous results.A total of 5 reports involving 410 patients with HCC were enrolled. The high expression of SNHG16 indicated worse overall survival (hazard ratio, 2.10; 95% CI, 1.22-3.60; P = .007) and disease-free survival (hazard ratio, 3.38; 95% CI, 1.10-10.40; P = .03). Additionally, the high expression of SNHG16 predicted a larger tumor size, metastasis, and advanced TNM stage.SNHG16 could serve as a potential biomarker of poor prognosis in HCC.


Assuntos
Carcinoma Hepatocelular/metabolismo , Neoplasias Hepáticas/metabolismo , RNA Longo não Codificante/genética , Biomarcadores Tumorais/genética , Carcinoma Hepatocelular/patologia , Humanos , Neoplasias Hepáticas/patologia , Prognóstico
3.
BMC Pulm Med ; 21(1): 301, 2021 Sep 23.
Artigo em Inglês | MEDLINE | ID: mdl-34556083

RESUMO

BACKGROUND: Chronic obstructive pulmonary disease (COPD) exacerbations are heterogenous and profoundly impact the disease trajectory. Bioactive lipid lysophosphatidic acid (LPA) has been implicated in airway inflammation but the significance of LPA in COPD exacerbation is not known. The aim of the study was to investigate the utility of serum LPA species (LPA16:0, 18:0, 18:1, 18:2, 20:4) as biomarkers of COPD exacerbation. PATIENTS AND METHODS: LPA species were measured in the baseline placebo sera of a COPD randomized controlled trial. Tertile levels of each LPA were used to assign patients into biomarker high, medium, and low subgroups. Exacerbation rate and risk were compared among the LPA subgroups. RESULTS: The levels of LPA species were intercorrelated (rho 0.29-0.91). Patients with low and medium levels of LPA (LPA16:0, 20:4) had significantly higher exacerbation rate compared to the respective LPA-high patients [estimated rate per patient per year (95% CI)]: LPA16:0-low = 1.2 (0.8-1.9) (p = 0.019), LPA16:0-medium = 1.3 (0.8-2.0) (p = 0.013), LPA16:0-high = 0.5 (0.2-0.9); LPA20:4-low = 1.4 (0.9-2.1) (p = 0.0033), LPA20:4-medium = 1.2 (0.8-1.8) (p = 0.0089), LPA20:4-high = 0.4 (0.2-0.8). These patients also had earlier time to first exacerbation (hazard ratio (95% CI): LPA16:0-low = 2.6 (1.1-6.0) (p = 0.028), LPA16:0-medium = 2.7 (1.2-6.3) (p = 0.020); LPA20.4-low = 2.8 (1.2-6.6) (p = 0.017), LPA20:4-medium = 2.7 (1.2-6.4) (p = 0.021). Accordingly, these patients had a significant increased exacerbation risk compared to the respective LPA-high subgroups [odd ratio (95% CI)]: LPA16:0-low = 3.1 (1.1-8.8) (p = 0.030), LPA16:0-medium = 3.0 (1.1-8.3) (p = 0.031); LPA20:4-low = 3.8 (1.3-10.9) (p = 0.012), LPA20:4-medium = 3.3 (1.2-9.5) (p = 0.025). For the other LPA species (LPA18:0, 18:1, 18:2), the results were mixed; patients with low and medium levels of LPA18:0 and 18:2 had increased exacerbation rate, but only LPA18:0-low patients had significant increase in exacerbation risk and earlier time to first exacerbation compared to the LPA18:0-high subgroup. CONCLUSIONS: The study provided evidence of association between systemic LPA levels and exacerbation in COPD. Patients with low and medium levels of specific LPA species (LPA16:0, 20:4) had increased exacerbation rate, risk, and earlier time to first exacerbation. These non-invasive biomarkers may aid in identifying high risk patients with dysregulated LPA pathway to inform risk management and drug development.

4.
Anal Chem ; 93(30): 10477-10486, 2021 08 03.
Artigo em Inglês | MEDLINE | ID: mdl-34292723

RESUMO

Timely and effective diagnosis is of great significance for improving the survival rate of lung cancer patients. Although histopathology is the main diagnostic tool among the existing methods for lung cancer diagnosis, it is not suitable for high-risk groups, early lung cancer patients, patients with advanced-stage disease, and other situations wherein tumor tissues cannot be obtained. In view of this, we proposed an innovative lung cancer diagnosis method employing for the first time a microfluidic technology for high-efficiency isolation and high-throughput single-cell analysis of exfoliated tumor cells (ETCs) in sputum. This method fully combines the advantages of traditional sputum cytology and microfluidic technology and realizes the diagnosis of lung cancer by using a small amount of repeatable ETCs instead of the tumor tissue. This method is expected to provide a practical strategy for the non-invasive detection of lung cancer patients and lung cancer screening for high-risk groups.


Assuntos
Neoplasias Pulmonares , Escarro , Biópsia , Detecção Precoce de Câncer , Humanos , Neoplasias Pulmonares/diagnóstico , Análise de Célula Única
5.
Sex Med ; 9(4): 100386, 2021 Jul 14.
Artigo em Inglês | MEDLINE | ID: mdl-34273785

RESUMO

INTRODUCTION: Dehydroepiandrosterone sulfate (DHEAS) has been reported to be associated with sexual function and general psychological health respectively, however, no one has ever examined their mutual relationships in a single study. AIM: The aim of the present study was to find out whether DHEAS, general psychological health, and erectile function were all associated with each other. METHODS: A cross-sectional study was conducted on 34 patients with erectile dysfunction (ED) and 32 healthy controls (HC). The levels of serum DHEAS were assessed by chemiluminescence method. Erectile function and general psychological health were measured by International Index for Erectile Function-5 (IIEF-5) and General Health Questionnaire 20(GHQ-20) respectively. MAIN OUTCOME MEASURE: The primary outcome measure of this study was the mutual correlations of serum DHEAS levels, general psychological health and erectile function. RESULTS: Compared to HC, patients with ED had a significant lower serum levels of DHEAS (6.43 ± 2.70 µmol/L vs 9.48 ± 2.82 µmol/L, P < .001) and higher scores on GHQ-20 (35.06 ± 8.56 vs 24.97 ± 2.55, P < .001). Multivariate binary logistic regression showed that both serum levels of DHEAS (OR = 0.667, 95% CI = 0.512-0.869, P = .003) and psychological distress (scores of GHQ-20 > 28) (OR = 6.921, 95% CI = 1.821-26.305, P = .005) were significantly associated with ED. However, no significant association between psychological distress and serum levels of DHEAS was found (OR = 0.798, 95% CI = 0.623-1.021, P = .072) after controlling for ED. Partial correlation analysis revealed that both scores of GHQ-20 (r = -0.595, P < .001) and DHEAS (r = 0.450, P < .001) were significantly correlated with scores of IIEF-5, while no significant relationship was found between scores of GHQ-20 and DHEAS (r = 0.116, P = .363) after controlling for scores of IIEF-5 and age. CONCLUSION: Both serum levels of DHEAS and general psychological health are significantly associated with erectile dysfunction in sexually active adult men but the relationship between general psychological health and erectile function seems to be independent of DHEAS. Li K, Liang S, Shi Y, et al. The Relationships of Dehydroepiandrosterone Sulfate, Erectile Function and General Psychological Health. Sex Med 2021;XX:XXXXXX.

6.
Eur Radiol ; 2021 Jul 13.
Artigo em Inglês | MEDLINE | ID: mdl-34258636

RESUMO

OBJECTIVES: Stratification of microsatellite instability (MSI) status in patients with colorectal cancer (CRC) improves clinical decision-making for cancer treatment. The present study aimed to develop a radiomics nomogram to predict the pre-treatment MSI status in patients with CRC. METHODS: A total of 762 patients with CRC confirmed by surgical pathology and MSI status determined with polymerase chain reaction (PCR) method were retrospectively recruited between January 2013 and May 2019. Radiomics features were extracted from routine pre-treatment abdominal pelvic computed tomography (CT) scans acquired as part of the patients' clinical care. A radiomics nomogram was constructed using multivariate logistic regression. The performance of the nomogram was evaluated using discrimination, calibration, and decision curves. RESULTS: The radiomics nomogram incorporating radiomics signatures, tumor location, patient age, high-density lipoprotein expression, and platelet counts showed good discrimination between patients with non-MSI-H and MSI-H, with an area under the curve (AUC) of 0.74 [95% CI, 0.68-0.80] in the training cohort and 0.77 [95% CI, 0.68-0.85] in the validation cohort. Favorable clinical application was observed using decision curve analysis. The addition of pathological characteristics to the nomogram failed to show incremental prognostic value. CONCLUSIONS: We developed a radiomics nomogram incorporating radiomics signatures and clinical indicators, which could potentially be used to facilitate the individualized prediction of MSI status in patients with CRC. KEY POINTS: • There is an unmet need to non-invasively determine MSI status prior to treatment. However, the traditional radiological evaluation of CT is limited for evaluating MSI status. • Our non-invasive CT imaging-based radiomics method could efficiently distinguish patients with high MSI disease from those with low MSI disease. • Our radiomics approach demonstrated promising diagnostic efficiency for MSI status, similar to the commonly used IHC method.

7.
J Atheroscler Thromb ; 2021 Jul 22.
Artigo em Inglês | MEDLINE | ID: mdl-34305082

RESUMO

AIM: To identify the association between serum beta-2-microglobulin (B2M) or cystatin C (CysC) and asymptomatic carotid atherosclerosis in patients with primary aldosteronism (PA). METHODS: In this cross-sectional study, 265 subjects were enrolled, including 83 patients with PA, 91 with essential hypertension (EH), and 91 normotensive (NT) controls. B2M, CysC, plasma renin activity (PRA), and plasma aldosterone concentration (PAC) were measured, and the aldosterone-to-renin ratio (ARR) was calculated. Carotid intima-media thickness (cIMT), increased cIMT, and presence of carotid plaque or carotid stenosis <50% in the carotid artery were measured via ultrasonography to evaluate the degree of asymptomatic carotid atherosclerosis. RESULTS: CIMT increased in the NT, EH, and PA groups (0.60 (0.50, 0.80) mm vs. 0.80 (0.60, 1.00) mm vs. 0.90 (0.70, 1.10) mm, P<0.01), so as the prevalence of increased cIMT and presence of carotid plaque (both P <0.05). The B2M and CysC levels exhibited the same trend (B2M: 1.60±0.34 mg/L, 1.80±0.41 mg/L, 1.98± 0.64 mg/L, P<0.05; CysC: 0.76±0.12 mg/L, 0.88±0.17 mg/L, 0.94±0.23 mg/L, P<0.05). B2M, CysC, PAC, and ARR were all positively associated with cIMT (all P<0.01) in the PA group. After adjusting for potential confounders, B2M, PAC, but not CysC or ARR were independently associated with increased cIMT and presence of carotid plaque and carotid stenosis <50%, respectively. The receiver operating characteristic (ROC) curve analysis revealed that B2M and PAC demonstrated significant predictive ability for increased cIMT and presence of carotid plaque and carotid stenosis <50%. CONCLUSION: B2M is an independent risk factor for asymptomatic carotid atherosclerosis in patients with PA.

8.
Br J Radiol ; 94(1123): 20201400, 2021 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-33882248

RESUMO

OBJECTIVE: The purpose of this study was to determine fat/water signal ratios using the mDIXON Quant sequence, quantitatively assess fat infiltration in the penis, and explore its possible relationship with penile hardness and erectile dysfunction. METHODS: Routine pelvic MRI with the mDIXON Quant sequence was performed in 62 subjects, including 22 people in the normal group, 20 people in the normal erectile hardness group, and 20 people in the erectile dysfunction (ED) group. The fat/water signal ratio in the penis was measured using the mDIXON Quant sequence. Shear wave elastography was used to evaluate the hardness of the corpus cavernosa of the penis. RESULTS: The fat/water signal ratio of the corpus spongiosum was significantly lower than that of the corpus cavernosa in the normal group (p = 0.03) and ED group (p < 0.01). There was no significant difference in the fat/water signal ratios between the normal group and the normal erectile hardness group. Fat infiltration was significantly lower, and erectile hardness was significantly higher in the normal erectile hardness group than in the ED group, and the fat infiltration in the left and right corpus cavernosa was inversely proportional to the erectile hardness of the penis. CONCLUSION: This study suggests that mDIXON Quant can be used as a non-invasive, quantitative, and objective method for evaluating penile fat infiltration. This method could help diagnose penile fat infiltration in patients with erectile dysfunction and varying body mass indexes. Our results could also allow for a more accurate diagnosis and monitoring of erectile hardness function by quantitatively measuring penile fat infiltration. ADVANCES IN KNOWLEDGE: (1) The proton density fat fraction technology is a new tool for the objective, quantitative and non-invasive evaluation of penile fat infiltration. (2) The quantitative measurement of fat infiltration in the corpora cavernosa might help diagnose and monitor penile erection hardness and its function more accurately.


Assuntos
Tecido Adiposo/diagnóstico por imagem , Disfunção Erétil , Imageamento por Ressonância Magnética/métodos , Ereção Peniana , Pênis/diagnóstico por imagem , Adulto , Índice de Massa Corporal , Técnicas de Imagem por Elasticidade , Humanos , Masculino , Projetos Piloto , Estudos Retrospectivos
9.
Sci Rep ; 11(1): 6079, 2021 03 16.
Artigo em Inglês | MEDLINE | ID: mdl-33727605

RESUMO

Mutations in the GBA1 gene encoding glucocerebrosidase (GCase) are linked to Gaucher (GD) and Parkinson's Disease (PD). Since some GD and PD patients develop ocular phenotypes, we determined whether ocular phenotypes might result from impaired GCase activity and the corresponding accumulation of glucosylceramide (GluCer) and glucosylsphingosine (GluSph) in the Gba1D409V/D409V knock-in (Gba KI/KI; "KI") mouse. Gba KI mice developed age-dependent pupil dilation deficits to an anti-muscarinic agent; histologically, the iris covered the anterior part of the lens with adhesions between the iris and the anterior surface of the lens (posterior synechia). This may prevent pupil dilation in general, beyond an un-responsiveness of the iris to anti-muscarinics. Gba KI mice displayed atrophy and pigment dispersion of the iris, and occlusion of the iridocorneal angle by pigment-laden cells, reminiscent of secondary open angle glaucoma. Gba KI mice showed progressive thinning of the retina consistent with retinal degeneration. GluSph levels were increased in the anterior and posterior segments of the eye, suggesting that accumulation of lipids in the eye may contribute to degeneration in this compartment. We conclude that the Gba KI model provides robust and reproducible eye phenotypes which may be used to test for efficacy and establish biomarkers for GBA1-related therapies.

10.
J Am Soc Mass Spectrom ; 32(8): 1987-1997, 2021 Aug 04.
Artigo em Inglês | MEDLINE | ID: mdl-33754705

RESUMO

Lysophospholipids are bioactive signaling molecules derived from cell membrane glycerophospholipids or sphingolipids and are highly regulated under normal physiological conditions. Lysophosphatidic acids (LPAs) are a class of lysophospholipids that act on G-protein-coupled receptors to exert a variety of cellular functions. Dysregulation of phospholipase activity and consequently LPA synthesis in serum have been linked to inflammation, such as seen in chronic obstructive pulmonary disease (COPD). The accurate measurement of phospholipids is critical for evaluating their dysregulation in disease. In this study, we optimized experimental parameters for the sensitive measurement of LPAs. We validated the method based on matrix, linearity, accuracy, precision, and stability. An investigation into sample extraction processes emphasized that the common practice of including low concentration of hydrochloric acid in the extraction buffer causes an overestimation of lipid recovery. The liquid chromatography gradient was optimized to separate various lysophospholipid classes. After optimization, detection limits of LPA were sufficiently sensitive for subsequent analysis, ranging from 2 to 8 nM. The validated workflow was applied to a cohort of healthy donor and COPD patient sera. Eight LPA species were identified, and five unique species of LPA were quantified. Most LPA species increased significantly in COPD patients compared to healthy donors. The correlation between LPAs and other demographic parameters was further investigated in a sample set of over 200 baseline patient sera from a COPD clinical trial. For the first time, LPAs other than the two most abundant and readily detectable moieties are quantified in COPD patients using validated methods, opening the door to downstream biomarker evaluation in respiratory disease.

11.
Redox Biol ; 42: 101908, 2021 06.
Artigo em Inglês | MEDLINE | ID: mdl-33674250

RESUMO

miR-101-3p may play a therapeutic role in various tumours. However, its anti-tumour mechanism remains unclear, and a definitive strategy to treat tumour cells in vivo is lacking. The objective of this study was to investigate the inhibitory mechanism of miR-101-3p on tumour cells and to develop relevant nanomedicines for in vivo therapy. The expression levels of miR-101-3p and its target protein TBLR1 in tumour tissues and cells were detected, and their relationship with ferroptosis was clarified. Furthermore, the efficacy of nanocarriers in achieving in vivo therapeutic gene delivery was evaluated. Nanomedicine was further developed, with the anti-proliferative in vivo therapeutic effect validated using a subcutaneous xenograft cancer model. The expression level of miR-101-3p negatively correlated with clinical tumour size and TNM stage. miR-101-3p restores ferroptosis in tumour cells by directly targeting TBLR1, which in turn promotes apoptosis and inhibits proliferation. We developed nanomedicine that can deliver miR-101-3p to tumour cells in vivo to achieve ferroptosis recovery, as well as to inhibit in vivo tumour proliferation. The miR-101-3p/TBLR1 axis plays an important role in tumour ferroptosis. Nanopharmaceuticals that increase miR-101-3p levels may be effective therapies to inhibit tumour proliferation.


Assuntos
Ferroptose , Neoplasias Hepáticas , MicroRNAs , Apoptose , Linhagem Celular Tumoral , Proliferação de Células , Regulação Neoplásica da Expressão Gênica , Humanos , Neoplasias Hepáticas/genética , MicroRNAs/genética , Nanomedicina
12.
Nature ; 591(7848): 131-136, 2021 03.
Artigo em Inglês | MEDLINE | ID: mdl-33472215

RESUMO

Plasma membrane rupture (PMR) is the final cataclysmic event in lytic cell death. PMR releases intracellular molecules known as damage-associated molecular patterns (DAMPs) that propagate the inflammatory response1-3. The underlying mechanism of PMR, however, is unknown. Here we show that the cell-surface NINJ1 protein4-8, which contains two transmembrane regions, has an essential role in the induction of PMR. A forward-genetic screen of randomly mutagenized mice linked NINJ1 to PMR. Ninj1-/- macrophages exhibited impaired PMR in response to diverse inducers of pyroptotic, necrotic and apoptotic cell death, and were unable to release numerous intracellular proteins including HMGB1 (a known DAMP) and LDH (a standard measure of PMR). Ninj1-/- macrophages died, but with a distinctive and persistent ballooned morphology, attributable to defective disintegration of bubble-like herniations. Ninj1-/- mice were more susceptible than wild-type mice to infection with Citrobacter rodentium, which suggests a role for PMR in anti-bacterial host defence. Mechanistically, NINJ1 used an evolutionarily conserved extracellular domain for oligomerization and subsequent PMR. The discovery of NINJ1 as a mediator of PMR overturns the long-held idea that cell death-related PMR is a passive event.


Assuntos
Moléculas de Adesão Celular Neuronais/metabolismo , Morte Celular , Membrana Celular/metabolismo , Fatores de Crescimento Neural/metabolismo , Animais , Apoptose , Moléculas de Adesão Celular Neuronais/química , Moléculas de Adesão Celular Neuronais/genética , Morte Celular/genética , Feminino , Humanos , Macrófagos , Masculino , Camundongos , Mutação , Necrose , Fatores de Crescimento Neural/química , Fatores de Crescimento Neural/genética , Multimerização Proteica , Piroptose/genética
13.
Talanta ; 221: 121660, 2021 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-33076170

RESUMO

As a common plasma protein, alpha-fetoprotein (AFP) is widely applied as the tumor biomarker for the diagnosis of many cancers. To develop a low cost, high sensitive and high-throughput method for the determination of AFP is significant for the disease diagnosis. In this work, an immunoassay with sandwich-type structures was performed on a paper-based chip for the analysis of AFP. AFP could be captured by the primary antibodies which were immobilized on the paper by chitosan. On the secondary antibodies, the modified initiator DNAs could trigger the hybridization chain reaction to amplify the fluorescence signals for AFP. A laser-induced fluorescence detector coupled with an interface was applied to detect the targets on the paper-based chip. Under the optimized conditions, the detection limit for AFP was 1.0 pg/mL. For every test, the sample solution consumption only was 10 µL. Finally, the method was applied to determine the AFP in serum of normal person and hepatopaths with hepatic malignant tumor, chronic hepatitis B and other suspected liver diseases. The AFP could be found from all of the samples and the results were similar to that obtained by chemiluminescence immunoassay. The recoveries for AFP ranged from 93.8% to 106%, which indicated the method was reliable. The method based on paper chip had great potential in the application of AFP determination.


Assuntos
Imunoensaio , Hepatopatias/diagnóstico , Microfluídica , alfa-Fetoproteínas , Biomarcadores Tumorais , Humanos , Lasers , alfa-Fetoproteínas/análise
14.
Int J Clin Exp Pathol ; 13(9): 2381-2386, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33042347

RESUMO

Mucin-producing carcinomas are unusual primary malignancies of breast, and constitute about 1-4 percent of total breast cancer. The mammary mucin producing carcinomas are divided into 4 histologic subtypes according to WHO classification, including mucinous carcinoma, mucinous cystadenocarcinoma (MCA), columnar cell mucinous carcinoma (CCMC), and signet ring cell carcinoma. However, the synchronous primary MCA and CCMC of breast is a very rare case presentation. The case reported a 56-year-old female, who presented with right mammary lumps and nipple discharge about 1 year. Imaging examinations revealed multiple cystic and solid nodules in upper outer quadrant of right breast, associated with ectatic ducts. Serum levels of tumor markers were normal. Right mammary lumpectomy revealed mucinous carcinoma, modified radical mastectomy, and lymph node dissection were carried out. For neoplastic cells, ER and PR were positive, HER2 (1+) was negative, Ki67 was low expression (3-5%). There was no metastatic carcinoma in lymph nodes (0/8). Modified radical mastectomy and lymph node dissections were carried out. Tamoxifen was chosen for adjuvant therapy. After a 3 month follow up, the patient survived without recurrences and distant metastasis. We report the first synchronous primary MCA and CCMC of breast with molecular subtype of Luminal A.

15.
Nature ; 584(7821): 479-483, 2020 08.
Artigo em Inglês | MEDLINE | ID: mdl-32788728

RESUMO

Lipopolysaccharide (LPS) resides in the outer membrane of Gram-negative bacteria where it is responsible for barrier function1,2. LPS can cause death as a result of septic shock, and its lipid A core is the target of polymyxin antibiotics3,4. Despite the clinical importance of polymyxins and the emergence of multidrug resistant strains5, our understanding of the bacterial factors that regulate LPS biogenesis is incomplete. Here we characterize the inner membrane protein PbgA and report that its depletion attenuates the virulence of Escherichia coli by reducing levels of LPS and outer membrane integrity. In contrast to previous claims that PbgA functions as a cardiolipin transporter6-9, our structural analyses and physiological studies identify a lipid A-binding motif along the periplasmic leaflet of the inner membrane. Synthetic PbgA-derived peptides selectively bind to LPS in vitro and inhibit the growth of diverse Gram-negative bacteria, including polymyxin-resistant strains. Proteomic, genetic and pharmacological experiments uncover a model in which direct periplasmic sensing of LPS by PbgA coordinates the biosynthesis of lipid A by regulating the stability of LpxC, a key cytoplasmic biosynthetic enzyme10-12. In summary, we find that PbgA has an unexpected but essential role in the regulation of LPS biogenesis, presents a new structural basis for the selective recognition of lipids, and provides opportunities for future antibiotic discovery.


Assuntos
Membrana Celular/química , Proteínas de Escherichia coli/química , Proteínas de Escherichia coli/metabolismo , Escherichia coli/química , Escherichia coli/patogenicidade , Lipopolissacarídeos/química , Lipopolissacarídeos/metabolismo , Amidoidrolases/química , Amidoidrolases/metabolismo , Motivos de Aminoácidos , Membrana Externa Bacteriana/química , Membrana Externa Bacteriana/metabolismo , Sítios de Ligação , Membrana Celular/metabolismo , Estabilidade Enzimática , Escherichia coli/citologia , Escherichia coli/efeitos dos fármacos , Genes Essenciais , Hidrolases/química , Hidrolases/metabolismo , Lipídeo A/química , Lipídeo A/metabolismo , Lipopolissacarídeos/biossíntese , Testes de Sensibilidade Microbiana , Viabilidade Microbiana/efeitos dos fármacos , Modelos Moleculares , Fragmentos de Peptídeos/química , Fragmentos de Peptídeos/metabolismo , Fragmentos de Peptídeos/farmacologia , Periplasma/química , Periplasma/metabolismo , Ligação Proteica , Virulência
16.
Sci Rep ; 10(1): 11187, 2020 Jul 07.
Artigo em Inglês | MEDLINE | ID: mdl-32636462

RESUMO

The objective of this study is to optimize the process parameters for preparing polystyrene (PS) PM2.5 particles by supercritical antisolvent (SAS) method. Toluene was selected as the solvent and supercritical carbon dioxide (SC-CO2) was used as the antisolvent. The Box-Behnken design-response surface method was applied to investigate the effect of crystallizer pressure, PS massic concentration, flow ratio of CO2/solution and crystallizer temperature on the size and the distribution of PS particles, systematically. It is found that crystallizer temperature is the most significant variable on the size and the distribution of PS particles, followed by flow ratio of CO2/solution and PS massic concentration, and crystallizer pressure is the slightest significant factor. The particle size increases with the increase of crystallizer temperature. The optimum conditions are obtained as crystallizer pressure 9.8 MPa, PS massic concentration 1.6 wt%, flow ratio of CO2/solution 140 g/g and crystallizer temperature 309 K. Under these conditions, the PS particle with the size of 2.78 µm and a narrow size distribution has been prepared, meeting PM2.5 standard aerosols. The results suggest that it is feasible to produce PM2.5 standard aerosols by SAS.

17.
Ann Transl Med ; 8(6): 386, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-32355830

RESUMO

Background: This study set out to evaluate the clinical significance and diagnostic effectiveness of serological tests and real-time polymerase chain reactions (RT-PCR) in children of different age groups and disease durations infected with Mycoplasma pneumoniae (MP). Methods: Pediatric patients with lower respiratory tract infection (LRTI) confirmed by polymerase chain reaction (PCR) were enrolled and subjected to bronchoalveolar lavage fluid PCR (BALF-PCR) for MP infection. The diagnostic values of the serum immunoglobulin M (IgM) test, paired sera immunoglobulin G (IgG) test, RT PCR applied to nasopharyngeal aspirates (NPA-PCR), and combined IgM and NPA-PCR test were evaluated. Results: When BALF PCR was used as the gold standard, the MP positivity rate of combined IgM and NPA PCR was 78.85%in children aged 3-5 years. The positivity rates of IgM, NPA PCR, and combined IgM and NPA PCR in children older than 5 years were 71.21%, 72.72%, and 84.85%, respectively. The detection rate of combined IgM and NPA PCR was consistent with BALF PCR (Kappa =0.727). The MP positivity rates of combined IgM and NPA PCR at 1-2 weeks was as high as 91.11%, and was consistent with the BALF PCR (Kappa =0.756). Moreover, the positivity rates of IgM or NPA PCR at 2-3 weeks were 63.16%, and were consistent with each other (Kappa =0.771). Conclusions: Combined IgM and NPA PCR is the optimal test to confirm MP infection among children aged 3-5 years in cases with a disease duration of less than2 weeks, and either NPA PCR or IgM is recommended for children older than 5 years with a disease duration of 2-3 weeks. Keywords: Mycoplasma pneumoniae pneumonia (MPP); diagnosis; children; age; disease duration.

18.
Zhongguo Zhen Jiu ; 40(3): 257-61, 2020 Mar 12.
Artigo em Chinês | MEDLINE | ID: mdl-32270637

RESUMO

OBJECTIVE: To explore the clinical therapeutic effect of acupuncture combined with opioid drugs on moderate and severe cancer pain. METHODS: A total of 60 patients with cancer were randomized into an observation group and a control group, 30 cases in each group. Oxycodonehydrochloride prolonged-release tablet was taken orally in the control group. On the basis of the control group, acupuncture was applied at Hegu (LI 4), Neiguan (PC 6), Zusanli (ST 36), Sanyinjiao (SP 6), etc. Corresponding back-shu points, xi-cleft points and ashi points were selected additionally according to primary viscera and pain sites in the observation group. The treatment was given once a day for 2 weeks. Symptomatic and supportive treatment were implanted, and no other antalgic measures were given during the trial. The daily dosage of opioid drug and the adverse reactions were recorded in both groups. Karnofsky performance status (KPS) and quality of life (QOL) scale scores were compared before and after treatment. Numerical rating scale (NRS) score was calculated to evaluate the clinical therapeutic effect. RESULTS: Compared before treatment, the daily dosage of opioid drugs after treatment was obviously reduced in the observation group (P<0.01), and was obviously increased in the control group (P<0.05). The dosage of opioid drugs after treatment in the observation group was much less than the control group (P<0.01). After treatment, the KPS and QOL scores were increased in both groups (P<0.01), and the scores in the observation group were superior to the control group (P<0.01, P<0.05). The analgesic effective rate was 90.0% (27/30) in the observation group, which was superior to 76.7% (23/30) in the control group (P<0.05). The adverse reactions rate in the observation group was lower than the control group (P<0.01). CONCLUSION: Acupuncture combined with opioid drugs can effectively relieve the cancer pain, improve the performance status and quality of life in cancer patients, reduce the dosage of opioid drugs and adverse reactions rate.


Assuntos
Terapia por Acupuntura , Analgésicos Opioides/uso terapêutico , Dor do Câncer/terapia , Neoplasias/fisiopatologia , Pontos de Acupuntura , Humanos , Neoplasias/terapia , Qualidade de Vida , Resultado do Tratamento
19.
Zhen Ci Yan Jiu ; 45(4): 259-63, 2020 Apr 25.
Artigo em Chinês | MEDLINE | ID: mdl-32333528

RESUMO

OBJECTIVE: To observe the effect of moxibustion on cardiac function and expression of myocardial tumor suppressor protein p53, mammalian target of rapamycin (mTOR) and phosphorylated(p)-mTOR (excessive autophagy-associated proteins of cardiomyocytes) in rats with chronic heart failure (CHF), so as to explore its mechanisms underlying improvement of CHF. METHODS: SD rats were divided into blank control (n=11), model(n=8), autophagy activator (n=8), autophagy inhibitor (n=9) and moxibustion(n=9) groups. The CHF model was established by i.p. injection of Doxorubicin Hydrochloride (DOX, 1 mg/mL, 1-4 mg/kg) every other day. Moxibustion was applied to bilateral "Feishu" (BL13) and "Xinshu" (BL15) for 20 min, 5 times a week for 3 weeks. Rats of the autophagy activator group received gavage of Rapamycin (RAPA, 2 mg/kg) and those of the autophagy inhibitor group received i.p. injection of Methyladenine (3-MA, 15 mg/kg) 5 times a week for 3 weeks after successful modeling. The heart weight and body weight were measured to calculate heart mass index (HW/BW=heart weight ÷ body weight). Cardiac output (CO) and heart rate (HR) were measured by using a cardiac function meter. Serum N-terminal pro-brain natriuretic peptide (NT-pro BNP) content was assayed by using ELISA, and the expression of myocardial p53, p-mTOR and mTOR proteins was examined by Western blot. RESULTS: (1) Compared with the blank control group, the HR, HW/BW, NT-pro BNP content and p53 expression levels were significantly increased (P<0.01), and the CO and ratio of p-mTOR/mTOR were significantly decreased in the model group (P<0.01). (2) Compared with the model group, the HR, HW/BW and NT-pro BNP content of the autophagy inhibitor and moxibustion groups were significantly decreased (P<0.01, P<0.05), and CO and p-mTOR/mTOR ratio were significantly increased in both autophagy inhibitor and moxibustion groups (P<0.01). (3) Compared with the autophagy activator group, the levels of HR, HW/BW, NT-pro BNP and p53 in the autophagy inhibitor and moxibustion groups were significantly lower (P<0.01), and those of CO and p-mTOR/mTOR levels were significantly higher (P<0.01). CONCLUSION: Moxibustion, similar to the autophagy inhibitor, has a protective action on myocardium in CHF rats, which is possible by preventing over expression of myocardial autophagy-associated proteins during CHF.


Assuntos
Insuficiência Cardíaca , Moxibustão , Animais , Proteínas Relacionadas à Autofagia , Doença Crônica , Miócitos Cardíacos , Ratos , Ratos Sprague-Dawley
20.
Aging (Albany NY) ; 12(3): 2974-2991, 2020 02 09.
Artigo em Inglês | MEDLINE | ID: mdl-32039833

RESUMO

The lncRNA tumor suppressor candidate 8 (TUSC8) plays a critical role in the development of several cancers. However, the biological functions and underlying molecular mechanisms of TUSC8 with respect to breast cancer remain largely unclear. Here, we found that TUSC8 was significantly down-regulated in breast cancer tissues and its high expression predicted better prognosis of breast cancer patients. Functionally, knock-down of TUSC8 drastically promoted the proliferation, migration and invasion of breast cancer cells in vitro and facilitated tumorigenicity and metastasis in vivo. Mechanistically, the results of luciferase reporter, RIP and RNA pull-down assays proved that TUSC8 functioned as molecular sponge for miR-190b-5p. Furthermore, we showed that TUSC8 served as a competing endogenous RNA (ceRNA) of myosin regulatory light chain interacting protein (MYLIP) through competitively binding with miR-190b-5p and suppressed breast cancer metastasis through regulating the expression of epithelial-mesenchymal transition (EMT) related markers. Clinically, the receiver operating characteristic curve (ROC) analyses revealed that the combination usage of TUSC8 and MYLIP might become novel promising diagnostic biomarkers for breast cancer. Taken together, these results suggested that TUSC8 inhibited breast cancer growth and metastasis via miR-190b-5p/MYLIP axis, providing us new insights into developing potential therapeutic targets for breast cancer patients.


Assuntos
MicroRNAs/metabolismo , RNA Longo não Codificante/metabolismo , Animais , Neoplasias da Mama , Linhagem Celular Tumoral , Proliferação de Células , Feminino , Regulação Neoplásica da Expressão Gênica , Técnicas de Silenciamento de Genes , Humanos , Camundongos , Camundongos Nus , MicroRNAs/genética , Metástase Neoplásica , Neoplasias Experimentais , RNA Longo não Codificante/genética , Ubiquitina-Proteína Ligases
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