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1.
BMC Infect Dis ; 24(1): 853, 2024 Aug 22.
Artigo em Inglês | MEDLINE | ID: mdl-39174918

RESUMO

BACKGROUND: Non-tuberculous mycobacteria (NTM) are present widely in the natural environment and can invade the human body through the respiratory tract, gastrointestinal tract, and skin. Immunocompromised patients are particularly prone to infection, which primarily affects multiple organs, including the lungs, lymph nodes, and skin. However, cases of NTM bloodstream infections are rare. Here, we report a rare case of Mycobacterium marseillense bloodstream infection with concurrent skin fungal infection in a patient after kidney transplantation. Related literature was reviewed to enhance the understanding of this rare condition. CASE PRESENTATION: A 58-year-old male with a history of long-term steroid and immunosuppressant use after kidney transplantation presented with limb swelling that worsened over the past two months. Physical examination revealed redness and swelling of the skin in all four limbs, with a non-healing wound on the lower left limb. Skin tissue analysis by metagenomic next-generation sequencing (mNGS) and fungal culture indicated infection with Trichophyton rubrum. Blood culture results suggested infection with Mycobacterium marseillense. After receiving anti-NTM treatment, the patient's symptoms significantly improved, and he is currently undergoing treatment. CONCLUSION: Mycobacterium marseillense is a NTM. Gram staining suffered from misdetection, and the acid-fast staining result was positive. This bacterium was identified by mass spectrometry and mNGS analyses. Antimicrobial susceptibility tests for NTM were performed using the broth microdilution method. The results of the susceptibility test showed that Mycobacterium marseillense was sensitive to clarithromycin, an intermediary between moxifloxacin and linezolid. Bacterial clearance requires a combination of drugs and an adequate course of treatment. NTM bloodstream infections are relatively rare, and early identification and proactive intervention are key to their successful management.


Assuntos
Infecções por Mycobacterium não Tuberculosas , Humanos , Masculino , Pessoa de Meia-Idade , Infecções por Mycobacterium não Tuberculosas/microbiologia , Infecções por Mycobacterium não Tuberculosas/tratamento farmacológico , Dermatomicoses/microbiologia , Dermatomicoses/tratamento farmacológico , Transplante de Rim/efeitos adversos , Hospedeiro Imunocomprometido , Antibacterianos/uso terapêutico , Micobactérias não Tuberculosas/isolamento & purificação , Micobactérias não Tuberculosas/efeitos dos fármacos , Bacteriemia/microbiologia , Bacteriemia/tratamento farmacológico , Mycobacterium/isolamento & purificação , Mycobacterium/efeitos dos fármacos , Pele/microbiologia , Pele/patologia
2.
BMC Cardiovasc Disord ; 24(1): 354, 2024 Jul 12.
Artigo em Inglês | MEDLINE | ID: mdl-38992615

RESUMO

BACKGROUND: Hyperlipidemia damages vascular wall and serves as a foundation for diseases such as atherosclerosis, hypertension and stiffness. The NOD-like receptor family pyrin domain-containing 3 (NLRP3) inflammasome is implicated in vascular dysfunction associated with hyperlipidemia-induced vascular injury. Sodium tanshinone IIA sulfonate (STS), a well-established cardiovascular protective drug with recognized anti-inflammatory, antioxidant, and vasodilatory properties, is yet to be thoroughly investigated for its impact on vascular relaxant imbalance induced by hyperlipidemia. METHODS: In this study, we treated ApoE-knockout (ApoE-/-) mouse with STS and assessed the activation of the NLRP3 inflammasome, expression of MMP2/9, integrity of elastic fibers, and vascular constriction and relaxation. RESULTS: Our findings reveal that STS intervention effectively preserves elastic fibers, significantly restores aortic relaxation function in ApoE-/- mice, and reduces their excessive constriction. Furthermore, STS inhibits the phosphorylation of spleen tyrosine kinase (SYK), suppresses NLRP3 inflammasome activation, and reduces MMP2/9 expression. CONCLUSIONS: These results demonstrate that STS protects vascular relaxation against hyperlipidemia-induced damage through modulation of the SYK-NLRP3 inflammasome-MMP2/9 pathway. This research provides novel insights into the mechanisms underlying vascular relaxation impairment in a hyperlipidemic environment and uncovers a unique mechanism by which STS preserves vascular relaxation, offering valuable foundational research evidence for its clinical application in promoting vascular health.


Assuntos
Modelos Animais de Doenças , Inflamassomos , Metaloproteinase 2 da Matriz , Metaloproteinase 9 da Matriz , Camundongos Endogâmicos C57BL , Camundongos Knockout para ApoE , Proteína 3 que Contém Domínio de Pirina da Família NLR , Fenantrenos , Transdução de Sinais , Quinase Syk , Vasodilatação , Animais , Proteína 3 que Contém Domínio de Pirina da Família NLR/metabolismo , Inflamassomos/metabolismo , Quinase Syk/metabolismo , Metaloproteinase 2 da Matriz/metabolismo , Fenantrenos/farmacologia , Masculino , Metaloproteinase 9 da Matriz/metabolismo , Vasodilatação/efeitos dos fármacos , Hiperlipidemias/tratamento farmacológico , Hiperlipidemias/fisiopatologia , Vasodilatadores/farmacologia , Fosforilação , Camundongos , Aorta/efeitos dos fármacos , Aorta/fisiopatologia , Aorta/metabolismo , Aorta/enzimologia , Apolipoproteínas E
3.
Acta Biochim Biophys Sin (Shanghai) ; 56(6): 892-904, 2024 06 25.
Artigo em Inglês | MEDLINE | ID: mdl-38733164

RESUMO

Diabetes accelerates vascular senescence, which is the basis for atherosclerosis and stiffness. The activation of the NOD-like receptor family pyrin domain containing 3 (NLRP3) inflammasome and oxidative stress are closely associated with progressive senescence in vascular smooth muscle cells (VSMCs). The vascular protective effect of FGF21 has gradually gained increasing attention, but its role in diabetes-induced vascular senescence needs further investigation. In this study, diabetic mice and primary VSMCs are transfected with an FGF21 activation plasmid and treated with a peroxisome proliferator-activated receptor γ (PPARγ) agonist (rosiglitazone), an NLRP3 inhibitor (MCC950), and a spleen tyrosine kinase (SYK)-specific inhibitor, R406, to detect senescence-associated markers. We find that FGF21 overexpression significantly restores the level of catalase (CAT), vascular relaxation, inhibits the intensity of ROSgreen fluorescence and p21 immunofluorescence, and reduces the area of SA-ß-gal staining and collagen deposition in the aortas of diabetic mice. FGF21 overexpression restores CAT, inhibits the expression of p21, and limits the area of SA-ß-gal staining in VSMCs under high glucose conditions. Mechanistically, FGF21 inhibits SYK phosphorylation, the production of the NLRP3 dimer, the expression of NLRP3, and the colocalization of NLRP3 with PYCARD (ASC), as well as NLRP3 with caspase-1, to reverse the cleavage of PPARγ, preserve CAT levels, suppress ROSgreen density, and reduce the expression of p21 in VSMCs under high glucose conditions. Our results suggest that FGF21 alleviates vascular senescence by regulating the SYK-NLRP3 inflammasome-PPARγ-catalase pathway in diabetic mice.


Assuntos
Senescência Celular , Diabetes Mellitus Experimental , Fatores de Crescimento de Fibroblastos , Inflamassomos , Camundongos Endogâmicos C57BL , Músculo Liso Vascular , Proteína 3 que Contém Domínio de Pirina da Família NLR , PPAR gama , Transdução de Sinais , Quinase Syk , Animais , Proteína 3 que Contém Domínio de Pirina da Família NLR/metabolismo , Proteína 3 que Contém Domínio de Pirina da Família NLR/genética , Quinase Syk/metabolismo , Quinase Syk/genética , PPAR gama/metabolismo , PPAR gama/genética , Músculo Liso Vascular/metabolismo , Músculo Liso Vascular/patologia , Inflamassomos/metabolismo , Camundongos , Diabetes Mellitus Experimental/metabolismo , Diabetes Mellitus Experimental/genética , Diabetes Mellitus Experimental/patologia , Masculino , Fatores de Crescimento de Fibroblastos/metabolismo , Fatores de Crescimento de Fibroblastos/genética , Miócitos de Músculo Liso/metabolismo , Miócitos de Músculo Liso/patologia
4.
BMC Med ; 21(1): 510, 2023 12 21.
Artigo em Inglês | MEDLINE | ID: mdl-38129829

RESUMO

BACKGROUND: Exposure to general anesthesia influences neuronal functions during brain development. Recently, interneurons were found to be involved in developmental neurotoxicity by anesthetic exposure. But the underlying mechanism and long-term consequences remain elusive. METHODS: Pregnant mice received 2.5% sevoflurane for 6-h on gestational day 14.5. Pentylenetetrazole (PTZ)-induced seizure, anxiety- and depression-like behavior tests were performed in 30- and 60-day-old male offspring. Cortical interneurons were labeled using Rosa26-EYFP/-; Nkx2.1-Cre mice. Immunofluorescence and electrophysiology were performed to determine the cortical interneuron properties. Q-PCR and in situ hybridization (ISH) were performed for the potential mechanism, and the finding was further validated by in utero electroporation (IUE). RESULTS: In this study, we found that maternal sevoflurane exposure increased epilepsy susceptibility by using pentylenetetrazole (PTZ) induced-kindling models and enhanced anxiety- and depression-like behaviors in adolescent offspring. After sevoflurane exposure, the highly ordered cortical interneuron migration was disrupted in the fetal cortex. In addition, the resting membrane potentials of fast-spiking interneurons in the sevoflurane-treated group were more hyperpolarized in adolescence accompanied by an increase in inhibitory synapses. Both q-PCR and ISH indicated that CXCL12/CXCR4 signaling pathway downregulation might be a potential mechanism under sevoflurane developmental neurotoxicity which was further confirmed by IUE and behavioral tests. Although the above effects were obvious in adolescence, they did not persist into adulthood. CONCLUSIONS: Our findings demonstrate that maternal anesthesia impairs interneuron migration through the CXCL12/CXCR4 signaling pathway, and influences the interneuron properties, leading to the increased epilepsy susceptibility in adolescent offspring. Our study provides a novel perspective on the developmental neurotoxicity of the mechanistic link between maternal use of general anesthesia and increased susceptibility to epilepsy.


Assuntos
Epilepsia , Pentilenotetrazol , Humanos , Gravidez , Feminino , Camundongos , Animais , Masculino , Sevoflurano/metabolismo , Sevoflurano/farmacologia , Pentilenotetrazol/toxicidade , Pentilenotetrazol/metabolismo , Exposição Materna/efeitos adversos , Interneurônios/metabolismo , Epilepsia/induzido quimicamente
5.
Mol Ecol ; 32(20): 5463-5478, 2023 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-37638537

RESUMO

The major plant pest fall armyworm (FAW), Spodoptera frugiperda, is native to the Americas and has colonized Africa and Asia within the Eastern hemisphere since 2016, causing severe damage to multiple agricultural crop species. However, the genetic origin of these invasive populations requires more in-depth exploration. We analysed genetic variation across the genomes of 280 FAW individuals from both the Eastern hemisphere and the Americas. The global range-wide genetic structure of FAW shows that the FAW in America has experienced deep differentiation, largely consistent with the Z-chromosomal Tpi haplotypes commonly used to differentiate 'corn-strain' and 'rice-strain' populations. The invasive populations from Africa and Asia are different from the American ones and have a relatively homogeneous population structure, consistent with the common origin and recent spreading from Africa to Asia. Our analyses suggest that north- and central American 'corn-strain' FAW are the most likely sources of the invasion into the Eastern hemisphere. Furthermore, evidence based on genomic, transcriptomic and mitochondrial haplotype network analyses indicates an earlier, independent introduction of FAW into Africa, with subsequent migration into the recent invasive population.

6.
Am J Hematol ; 98(2): 251-263, 2023 02.
Artigo em Inglês | MEDLINE | ID: mdl-36309982

RESUMO

1q gain (+1q) is the most common high-risk cytogenetic abnormality (HRCA) in patients with multiple myeloma (MM). However, its prognostic value remains unclear in the era of novel agents. Here, we retrospectively analyzed the impact of +1q on the outcomes of 934 patients newly diagnosed with MM. +1q was identified in 53.1% of patients and verified as an independent variate for inferior overall survival (OS) (hazard ratio, 1.400; 95% confidence interval, 1.097-1.787; p = .007). Concurrence of other HRCAs (particularly t(14;16) and del(17p)) further exacerbated the outcomes of patients with +1q, suggesting prognostic heterogeneity. Thus, a risk-scoring algorithm based on four risk variates (t(14;16), hypercalcemia, ISS III, and high LDH) was developed to estimate the outcomes of patients with +1q. Of the patients, 376 evaluable patients with +1q were re-stratified into low (31.6%), intermediate (61.7%), and high risk (6.7%) groups, with significantly different progression-free survival and OS (p < .0001), in association with early relapse of the disease. The prognostic value of this model was validated in the CoMMpass cohort. While attaining undetectable MRD largely circumvented the adverse impact of +1q, it scarcely ameliorated the outcome of the patients with high risk, who likely represent a subset of patients with extremely poor survival. Hence, patients with +1q are a heterogeneous group of high-risk patients, therefore underlining the necessity for their re-stratification. The proposed simple risk-scoring model can estimate the outcomes of patients with +1q, which may help guide risk-adapted treatment for such patients.


Assuntos
Mieloma Múltiplo , Humanos , Prognóstico , Mieloma Múltiplo/diagnóstico , Mieloma Múltiplo/genética , Estudos Retrospectivos , Aberrações Cromossômicas , Modelos de Riscos Proporcionais
7.
BMC Med Imaging ; 23(1): 175, 2023 11 02.
Artigo em Inglês | MEDLINE | ID: mdl-37919642

RESUMO

BACKGROUND: UTE has been used to depict lung parenchyma. However, the insufficient discussion of its performance in pediatric pneumonia compared with conventional sequences is a gap in the existing literature. The objective of this study was to compare the diagnostic value of 3D-UTE with that of 3D T1-GRE and T2-FSE sequences in young children diagnosed with pneumonia. METHODS: Seventy-seven eligible pediatric patients diagnosed with pneumonia at our hospital, ranging in age from one day to thirty-five months, were enrolled in this study from March 2021 to August 2021. All patients underwent imaging using a 3 T pediatric MR scanner, which included three sequences: 3D-UTE, 3D-T1 GRE, and T2-FSE. Subjective analyses were performed by two experienced pediatric radiologists based on a 5-point scale according to six pathological findings (patchy shadows/ground-glass opacity (GGO), consolidation, nodule, bulla/cyst, linear opacity, and pleural effusion/thickening). Additionally, they assessed image quality, including the presence of artifacts, and evaluated the lung parenchyma. Interrater agreement was assessed using intraclass correlation coefficients (ICCs). Differences among the three sequences were evaluated using the Wilcoxon signed-rank test. RESULTS: The visualization of pathologies in most parameters (patchy shadows/GGO, consolidation, nodule, and bulla/cyst) was superior with UTE compared to T2-FSE and T1 GRE. The visualization scores for linear opacity were similar between UTE and T2-FSE, and both were better than T1-GRE. In the case of pleural effusion/thickening, T2-FSE outperformed the other sequences. However, statistically significant differences between UTE and other sequences were only observed for patchy shadows/GGO and consolidation. The overall image quality was superior or at least comparable with UTE compared to T2-FSE and T1-GRE. Interobserver agreements for all visual assessments were significant and rated "substantial" or "excellent." CONCLUSIONS: In conclusion, UTE MRI is a useful and promising method for evaluating pediatric pneumonia, as it provided better or similar visualization of most imaging findings compared with T2-FSE and T1-GRE. We suggest that the UTE MRI is well-suited for pediatric population, especially in younger children with pneumonia who require longitudinal and repeated imaging for clinical care or research and are susceptible to ionizing radiation.


Assuntos
Cistos , Derrame Pleural , Pneumonia , Pré-Escolar , Humanos , Recém-Nascido , Vesícula , Imageamento Tridimensional/métodos , Imageamento por Ressonância Magnética/métodos , Pneumonia/diagnóstico por imagem , Lactente
8.
BMC Med Imaging ; 22(1): 119, 2022 07 04.
Artigo em Inglês | MEDLINE | ID: mdl-35787673

RESUMO

OBJECT: To explore the feasibility and clinical application of AI -assisted compressed sensing (ACS) technology in kidney MR imaging. METHODS: 33 patients were enrolled in this study, affiliated to our hospital from September 2020 to April 2021. The patients underwent T2-weighed sequences of both the ACS scan and the conventional respiratory navigator (NAVI) scan. We evaluated the subjective image quality scores, including the sharpness of image edge, artifact and the overall image quality, and compared the objective image quality indicators such as scanning time, signal-to-noise ratio (SNR), and contrast signal-to-noise ratio (CNR). The Wilcoxon's rank sum test and the paired t test were used to compare the image quality between ACS and NAVI groups. The p-value less than 0.05 indicated a statistically significant difference. RESULTS: The edge sharpness of the ACS group was significant lower than that of the NAVI group (p < 0.01), however, there were no significant differences in the artifact and the overall rating of image quality between the two groups (p > 0.05). In terms of the objective image quality scores, the scanning time of the ACS group is significantly lower than that of control group. The SNR and CNR of ACS group were significantly higher than those of NAVI group (SNR:3.63 ± 0.76 vs 3.04 ± 0.44, p < 0.001; CNR: 14.44 ± 4.53 vs 12.05 ± 3.32, p < 0.001). In addition, the subjective and objective measurement results of the two radiologists were in good agreement (ICC = 0.61-0.88). CONCLUSION: ACS technology has obvious advantages when applied to kidney MR imaging, which can realize ultra-fast MR imaging. The images can be acquired with a single breath-hold (17 s), which greatly shortens the scanning time. Moreover, the image quality is equal to or better than the conventional technology, which can meet the diagnostic requirements. Thus, it has obvious advantages in diagnosis for kidney disease patients with different tolerance levels for the clinical promotion.


Assuntos
Rim , Imageamento por Ressonância Magnética , Inteligência Artificial , Estudos de Viabilidade , Humanos , Rim/diagnóstico por imagem , Tecnologia
9.
Photochem Photobiol Sci ; 20(8): 1087-1098, 2021 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-34398442

RESUMO

In this study, C-doped TiO2 nanoparticles (C-TiO2) were prepared and tested as a photosensitizer for visible-light-driven photodynamic therapy against cervical cancer cells (HeLa). X-ray diffraction and Transmission Electron Microscopy confirmed the anatase form of nanoparticles, spherical shape, and size distribution from 5 to 15 nm. Ultraviolet-visible light spectroscopy showed that C doping of TiO2 enhances the optical absorption in the visible light range caused by a bandgap narrowing. The photo-cytotoxic activity of C-TiO2 was investigated in vitro against HeLa cells. The lack of dark cytotoxicity indicates good biocompatibility of C-TiO2. In contrast, a combination with blue light significantly reduced the survival of HeLa cells: illumination only decreased cell viability by 30% (15 min of illumination, 120 µW power), and 60% when HeLa cells were preincubated with C-TiO2. We have also confirmed blue light-induced C-TiO2-catalyzed generation of reactive oxygen species in vitro and intracellularly. Oxidative stress triggered by C-TiO2/blue light was the leading cause of HeLa cell death. Fluorescent labeling of treated HeLa cells showed distinct morphological changes after the C-TiO2/blue light treatment. Unlike blue light illumination, which caused the appearance of large necrotic cells with deformed nuclei, cytoplasm swelling, and membrane blebbing, a combination of C-TiO2/blue light leads to controlled cell death, thus providing a better outcome of local anticancer therapy.


Assuntos
Carbono/química , Nanopartículas , Fototerapia , Titânio/química , Titânio/farmacologia , Neoplasias do Colo do Útero/patologia , Sobrevivência Celular/efeitos dos fármacos , Sobrevivência Celular/efeitos da radiação , Terapia Combinada , Feminino , Células HeLa , Humanos
10.
J Perinat Med ; 49(2): 237-240, 2021 Feb 23.
Artigo em Inglês | MEDLINE | ID: mdl-33470960

RESUMO

OBJECTIVES: The coronavirus disease 2019 (COVID-19) had become a worldwide pandemic, however, information is limited on the asymptomatic proportion and thromboembolism risk of pregnant women with infection. METHODS: All 32 pregnant women with COVID-19 who were admitted to the hospital in Wuhan during the outbreak from January 20 to March 18, 2020, were retrospectively reviewed for the clinical records, laboratory tests, chest CT scans, and neonatal outcomes. RESULTS: There were 17 of the 32 patients (53%) with no subjective symptoms before admission, and 13 (41%) remained asymptomatic throughout hospitalization. There were 28 patients (88%) showing typical radiographic evidence of pneumonia on chest CT. The patients with COVID-19 were found in an increased risk of thromboembolism with much higher D-dimer levels than uninfected pregnant women. One neonate with asphyxia and positive immunoglobulin M (IgM) and immunoglobulin G (IgG) antibodies was reported. CONCLUSIONS: The considerable asymptomatic proportion of pregnant women with COVID-19 indicates symptom-based screening would miss a number of cases. Chest CT could provide a useful screening resource during the COVID-19epidemic outbreak. Anticoagulation therapy for the postpartum patients may be helpful for good prognosis. The findings provide important information for the hospital isolation, control strategies and clinical therapy.


Assuntos
Infecções Assintomáticas/epidemiologia , COVID-19/complicações , Complicações Infecciosas na Gravidez/virologia , Tromboembolia/virologia , Adulto , COVID-19/sangue , COVID-19/diagnóstico por imagem , COVID-19/epidemiologia , China/epidemiologia , Feminino , Produtos de Degradação da Fibrina e do Fibrinogênio/metabolismo , Humanos , Recém-Nascido , Gravidez , Complicações Infecciosas na Gravidez/sangue , Complicações Infecciosas na Gravidez/diagnóstico por imagem , Complicações Infecciosas na Gravidez/epidemiologia , Radiografia Torácica , Estudos Retrospectivos , Tomografia Computadorizada por Raios X , Adulto Jovem
11.
J Antimicrob Chemother ; 75(7): 1850-1858, 2020 07 01.
Artigo em Inglês | MEDLINE | ID: mdl-32154866

RESUMO

OBJECTIVES: To evaluate in vitro activity of the novel ß-lactamase boronate inhibitor taniborbactam (VNRX-5133) combined with cefepime or meropenem against 500 urinary Gram-negative bacilli. METHODS: Cefepime/taniborbactam and 14 comparators were tested by broth microdilution or agar dilution methods. A total of 450 Enterobacteriaceae and 50 Pseudomonas aeruginosa were selected from 2017 to 2019 based on different ß-lactamase-producing or resistance phenotypes. For carbapenem-non-susceptible isolates, the modified carbapenem inactivation method (mCIM), EDTA-CIM (eCIM) and amplification of carbapenemase genes were performed. For NDM-producing isolates and those with cefepime/taniborbactam MICs >8 mg/L, the MICs of meropenem/taniborbactam and/or mutations in PBP3 were investigated. RESULTS: Taniborbactam improved cefepime activity with the same efficiency as avibactam improved ceftazidime activity against 66 KPC-2 producers, 30 non-carbapenemase-producing carbapenem-non-susceptible Enterobacteriaceae and 28 meropenem-susceptible P. aeruginosa. However, cefepime/taniborbactam exhibited more potent activity than ceftazidime/avibactam against 56 ESBL-producing, 61 AmpC-producing, 32 ESBL and AmpC co-producing, 87 NDM-producing and 21 MBL-producing Enterobacteriaceae predicted by phenotypic mCIM and eCIM, 82 Enterobacteriaceae that were susceptible to all tested ß-lactams and 22 carbapenem-non-susceptible P. aeruginosa. A four-amino acid 'INYR' or 'YRIN' insertion, with or without a one/two-amino acid mutation in PBP3, may have caused cefepime/taniborbactam MICs >8 mg/L among 96.6% (28/29) of the NDM-5-producing Escherichia coli, which accounted for the majority of isolates with cefepime/taniborbactam MICs >8 mg/L (76.1%, 35/46). CONCLUSIONS: Taniborbactam's superior breadth of activity, when paired with cefepime or meropenem, suggests these ß-lactam/ß-lactamase inhibitor combinations could be promising candidates for treating urinary tract infections caused by ESBL and/or AmpC, KPC or NDM-producing Enterobacteriaceae or P. aeruginosa.


Assuntos
Antibacterianos , Inibidores de beta-Lactamases , Antibacterianos/farmacologia , Compostos Azabicíclicos/farmacologia , Ácidos Borínicos , Ácidos Carboxílicos , Cefepima , Ceftazidima , China , Combinação de Medicamentos , Meropeném/farmacologia , Testes de Sensibilidade Microbiana , Inibidores de beta-Lactamases/farmacologia , beta-Lactamases/genética
12.
Pharmacol Res ; 157: 104846, 2020 07.
Artigo em Inglês | MEDLINE | ID: mdl-32339784

RESUMO

Doxorubicin (DOX) is one of the most effective antineoplastic drugs. However, its clinical application has been greatly limited due to the development of cardiotoxicity with DOX utilization. A number of theories have been postulated for DOX-induced cardiotoxicity with a pivotal contribution from unchecked (excess) mitophagy and mitochondrial fission. Liensinine (LIEN), a newly identified mitophagy inhibitor, strengthens the antineoplastic efficacy of DOX although its action on hearts remains elusive. This study was designed to examine the effect of LIEN on DOX-induced cardiotoxicity and the underlying mechanisms involved with a focus on mitochondrial dynamics. Our data revealed that LIEN alleviated DOX-induced cardiac dysfunction and apoptosis through inhibition of dynamin-related protein 1 (Drp1)-mediated excess (unchecked) mitochondrial fission. LIEN treatment decreased Drp1 phosphorylation at Ser616 site, inhibited mitochondrial fragmentation, mitophagy (assessed by TOM20 and TIM23), oxidative stress, cytochrome C leakage, cardiomyocyte apoptosis, as well as improved mitochondrial function and cardiomyocyte contractile function in DOX-induced cardiac injury. In DOX-challenged neonatal mouse ventricular myocytes (NMVMs), LIEN-suppressed Drp1 phosphorylation, mitochondrial fragmentation, and apoptosis were blunted by Rab7 overexpression, the effect of which was reversed by the ERK inhibitor U0126. Moreover, activation of ERK or Drp1 abolished the protective effects of LIEN on cardiomyocyte mechanical anomalies. These data shed some lights towards understanding the role of LIEN as a new protective agent against DOX-associated cardiotoxicity without compromising its anti-tumor effects.


Assuntos
Dinaminas/metabolismo , Cardiopatias/prevenção & controle , Isoquinolinas/farmacologia , Mitocôndrias Cardíacas/efeitos dos fármacos , Dinâmica Mitocondrial/efeitos dos fármacos , Mitofagia/efeitos dos fármacos , Miócitos Cardíacos/efeitos dos fármacos , Fenóis/farmacologia , Animais , Apoptose/efeitos dos fármacos , Sinalização do Cálcio , Cardiotoxicidade , Modelos Animais de Doenças , Doxorrubicina , Dinaminas/genética , MAP Quinases Reguladas por Sinal Extracelular/metabolismo , Cardiopatias/induzido quimicamente , Cardiopatias/metabolismo , Cardiopatias/patologia , Camundongos , Mitocôndrias Cardíacas/metabolismo , Mitocôndrias Cardíacas/patologia , Miócitos Cardíacos/metabolismo , Miócitos Cardíacos/patologia , Fosforilação , Proteínas rab de Ligação ao GTP/genética , Proteínas rab de Ligação ao GTP/metabolismo , proteínas de unión al GTP Rab7
16.
Int J Mol Sci ; 18(2)2017 Jan 27.
Artigo em Inglês | MEDLINE | ID: mdl-28134809

RESUMO

The interrelationship between ionizing radiation and the immune system is complex, multifactorial, and dependent on radiation dose/quality and immune cell type. High-dose radiation usually results in immune suppression. On the contrary, low-dose radiation (LDR) modulates a variety of immune responses that have exhibited the properties of immune hormesis. Although the underlying molecular mechanism is not fully understood yet, LDR has been used clinically for the treatment of autoimmune diseases and malignant tumors. These advancements in preclinical and clinical studies suggest that LDR-mediated immune modulation is a well-orchestrated phenomenon with clinical potential. We summarize recent developments in the understanding of LDR-mediated immune modulation, with an emphasis on its potential clinical applications.


Assuntos
Hormese/efeitos da radiação , Sistema Imunitário/efeitos da radiação , Animais , Relação Dose-Resposta à Radiação , Humanos , Modelos Biológicos
17.
Int J Cancer ; 139(10): 2157-68, 2016 11 15.
Artigo em Inglês | MEDLINE | ID: mdl-27299986

RESUMO

It has been generally accepted that both natural and man-made sources of ionizing radiation contribute to human exposure and consequently pose a possible risk to human health. However, accumulating evidence has shown that the biological effects of low-dose radiation (LDR) are different from those of high-dose radiation. LDR can stimulate proliferation of normal cells and activate their defense systems, while these biological effects are not observed in some cancer cell types. Although there is still no concordance on this matter, the fact that LDR has the potential to enhance the effects of cancer therapeutics and reduce the toxic side effects of anti-cancer therapy has garnered significant interest. Here, we provide an overview of the current knowledge regarding the experimental data detailing the different responses of normal and cancer tissues to LDR, the underlying mechanisms, and its significance in clinical application.


Assuntos
Neoplasias/radioterapia , Animais , Proliferação de Células/efeitos da radiação , Relação Dose-Resposta à Radiação , Hormese/efeitos da radiação , Humanos , Sistema Imunitário/efeitos da radiação , Neoplasias/imunologia
18.
Tumour Biol ; 37(5): 6297-306, 2016 May.
Artigo em Inglês | MEDLINE | ID: mdl-26619847

RESUMO

Drugs targeting the vascular endothelial growth factor (VEGF) and its receptor (VEGFR) signaling (anti-VEGF/VEGFR drugs) are the most validated anti-angiogenic strategies for cancer treatment. Complete response (CR) is a rare event in cancer patients receiving chemotherapy. A meta-analysis was conducted to determine whether adding anti-VEGF/VEGFR drugs to chemotherapy can further increase the chance of CR in the first-line therapy. Relevant databases were systematically searched for the period 2000-2015. Eligible studies were selected according to Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement. The incidence, relative risk (RR), and 95 % confidence intervals (CIs) were calculated using random-effects or fixed-effects models based on the heterogeneity of selected studies. A total of 12,453 patients from 28 randomized controlled trials were included. The overall incidence of CR in patients treated with anti-VEGF/VEGFR drugs plus chemotherapy was 1.5 % (95 % CI, 1.0-2.0 %) compared to 1.1 % (95 % CI, 0.7-1.4 %) in the chemotherapy-alone arm. Adding anti-VEGF/VEGFR drugs was associated with significant improvement of CR (RR, 1.52, 95 % CI, 1.18-1.95, P = 0.001). When stratified by drug type, adding VEGFR tyrosin kinase inhibitors (TKIs) did not increase the chance of CR (RR, 0.87, 95 % CI, 0.51-1.49; P = 0.614). The addition of bevacizumab with 7.5 mg/kg every 3 weeks, but not 15 mg/kg every 3 weeks, significantly improves the CR (7.5 mg, RR, 2.43, 95 % CI, 1.64-3.60, P = 0.000; 15 mg, RR, 1.07, 95 % CI, 0.63-1.81, P = 0.799). In subgroup analysis, a significant improvement of CR by the addition of anti-VEGF/VEGFR drugs was observed in patients with colorectal cancer (RR, 2.10, 95 % CI 1.21-3.63, P = 0.008), ovarian cancer (RR, 3.07; 95 % CI, 1.68-5.62, P = 0.000), and patients who are treated with platinum-based regimens (RR, 1.78, 95 % CI, 1.23-2.59, P = 0.002). Low-dose bevacizumab, rather than VEGFR TKIs or high-dose bevacizumab, can increase the chance of CR in patients receiving chemotherapy.


Assuntos
Neoplasias/tratamento farmacológico , Inibidores de Proteínas Quinases/administração & dosagem , Fator A de Crescimento do Endotélio Vascular/genética , Receptor 1 de Fatores de Crescimento do Endotélio Vascular/genética , Inibidores da Angiogênese/administração & dosagem , Anticorpos Monoclonais Humanizados/administração & dosagem , Protocolos de Quimioterapia Combinada Antineoplásica , Bevacizumab/administração & dosagem , Humanos , Neoplasias/genética , Neoplasias/patologia , Ensaios Clínicos Controlados Aleatórios como Assunto , Fator A de Crescimento do Endotélio Vascular/antagonistas & inibidores , Receptor 1 de Fatores de Crescimento do Endotélio Vascular/antagonistas & inibidores
20.
Zhong Yao Cai ; 37(11): 1919-24, 2014 Nov.
Artigo em Chinês | MEDLINE | ID: mdl-26027109

RESUMO

OBJECTIVE: To investigate the distribution characteristics of mineral elements in the soil of Angelica sinensis producing regions and its relationship with altitude and soil types. METHODS: The contents of 15 mineral elements in 103 batches of soil from 13 counties were determined by ICP-MS or AAS. Pearson correlation analysis, partial correlation analysis and systematical cluster analysis were used to analyze the data. RESULTS: Pearson correlation analysis showed that the content of Mg in soil and altitude showed significant positive correlation(P <0. 01), the content of Cd in soil and altitude showed significant negative correlation(P <0. 05), and the con- tents of Pb, Cd, As, Cu, Cr as well as Ni in soil and altitude showed negative correlation. The result of systematic cluster analysis showed that 103 batches of soil were clustered into 5 groups. The main soil types of group I were black soil, haplic kastanozems and black sandy-soil, group II was loess, group III was cinnamon soil, group IV were red soil and grey cinnamon soil, and group V were black soil, haplic kastanozems, grey cinnamon soil and cinnamon soil. CONCLUSION: The distribution of mineral elements in soil is closely related to altitude and soil types.


Assuntos
Altitude , Angelica sinensis , Minerais/análise , Solo/química
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