RESUMO
Malaria, caused by the genus Plasmodium, remains a global public health concern. It is estimated by the World Health Organization that over 40% of the world's population lives in areas at risk for malarial transmission, and around half a million people succumb to this infectious disease annually, which is related to the rapid spread of drug-resistant parasite strains. Indole derivatives, which possess broad-spectrum pharmacological properties, play a crucial role in the discovery of new drugs. Many indole derivatives exhibited potential in vitro and in vivo activity against both drug-sensitive and drug-resistant malaria, suggesting that the indole moiety is a useful template for the development of novel antimalarial agents. This review outlines the advances in indole alkaloids and hybrids with antimalarial potential in the recent decade.
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Antimaláricos/farmacologia , Alcaloides Indólicos/farmacologia , Malária/tratamento farmacológico , Plasmodium/efeitos dos fármacos , Animais , Antimaláricos/química , Resistência a Medicamentos , Interações Hospedeiro-Parasita , Humanos , Alcaloides Indólicos/química , Malária/parasitologia , Estrutura Molecular , Plasmodium/patogenicidade , Relação Estrutura-AtividadeRESUMO
BACKGROUND: Panic disorder (PD), major depressive disorder (MDD), and the comorbidity (PD&MDD) in college students have caused a heavy disease burden for individuals and families. However, little was known for the comorbidity, especially the impact of parental rearing style on the incidence of the PD&MDD comorbidity. METHODS: A cohort study was conducted among 6652 Chinese college students. Composite International Diagnostic Interview (CIDI-3.0) was used for disease diagnosis. The parental rearing styles were measured by the Egna Minnen Beträffande Uppfostran (EMBU) scale and factor analysis was used to reduce the dimension of the EMBU scale. Multinomial logistic regression models were used to determine the relationships between parenting styles and disease incidence. SPSS version 26.0 was used for all statistical analyses. RESULTS: The 1-year incidence of PD, MDD, and PD&MDD comorbidity was 0.27 %, 2.04 %, and 0.21 %, respectively. Emotional warmth mode (OR = 0.753, 95%CI: 0.631-0.899, P < 0.01) were only negatively correlated with major depressive disorder. However, punishment denial mode (OR = 1.857, 95%CI: 1.316-2.620, P < 0.01) and over-participation mode (OR = 1.862, 95%CI: 1.176-2.949, P < 0.01) were positively correlated with the comorbidity of panic disorder and major depressive disorder. LIMITATIONS: The limited follow-up period was only 1 year in this study which had impacted the collection of new onset cases. CONCLUSIONS: Parental rearing style has a long-term influence on the psychiatric status of college students. Parenting style interventions working as the second level of mental disorder prevention will play an important role in MDD, PD and comorbidity prevention.
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Transtorno Depressivo Maior , Transtorno de Pânico , Humanos , Transtorno de Pânico/epidemiologia , Transtorno de Pânico/diagnóstico , Transtorno Depressivo Maior/epidemiologia , Estudos de Coortes , Incidência , Pais/psicologia , Estudantes , ComorbidadeRESUMO
BACKGROUND: This study aims to assess the value of two-dimensional speckle tracking imaging (2D-STI) combined with real-time 3-dimensional echocardiography (RT-3DE) in evaluating left heart function in patients with combined ETH and PAF. METHODS: A prospective study was designed, and the research period was from January 2017 to January 2020. A PAF observation group comprised of patients with ETH and PAF, a PAF control group of patients with ETH but without PAF, and a healthy volunteer group referred to as the healthy group, each comprised of 50 patients was established. All patients underwent routine ultrasound imaging examination using 2D-STI and RT-3DE. The interventricular septum thickness (IVST), left and right atrioventricular diameter (LAD), left ventricular posterior wall thickness (PWT), left ventricular ejection fraction (LVEF), the mean left atrium peak strain (mSs, mSe, mSa), strain rate (mSRs, mSRe, mSRa), the left ventricular mass (LVM), left ventricular mass index (LVMI), and left atrial total emptying volume (LATEV), the left atrial volume index (LAVI), left atrial total emptying fraction (LATEF), left atrium expansion index (LAEI), left atrium passive ejection fraction (LAPEF), and left atrial active ejection fraction (LAAEF) were calculated. Patients in the PAF observation group received telmisartan combined with rosuvastatin after diagnosis and 12- and 24-month-follow up visits were conducted. During these visits, 2D-STI combined with RT-3DE was used to evaluate cardiac function and each patient's blood pressure was monitored. RESULTS: Patients in the PAF observation group had a significantly longer course of ETH than patients in the PAF control group (13.5±4.4 vs. 10.32±5.6, P=0.002). The comparison of routine 2D-STI and RT-3DE ultrasound indexes among the three groups also showed significant differences (P<0.01). During the 2-year follow-up period, the IVST, LAD, PWT, and LVEF of remaining patients significantly improved as treatment progressed (P<0.05). The LAVI, LATEF, and LAEI also improved significantly as the treatment progressed (P<0.05). After 12 months of treatment, the recurrence rate of atrial fibrillation was 16.33% (8/45) and after 24 months this was 34.21% (13/38). CONCLUSIONS: Cardiac function could be evaluated comprehensively by 2D-STI combined with RT-3DE in patients with ETH combined with PAF at initial diagnosis and follow-up.
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OBJECTIVE: To investigate the HIV-1 drug resistance associated mutations and examine the susceptibility of HIV-1 with these mutations to antiretroviral in treatment-naive individuals in Liaoning province from 2004 to 2008. METHODS: RNA was extracted from 20 plasma samples of diagnosed untreated HIV-1-infected treatment-naive patients by drawing method. After the viral loading (VL) test, the protease and nucleoside reverse transcriptase coding regions were amplified by RT-PCR, nested PCR and sequence analysis directly. Levels of resistance and prevalence were evaluated according to the Stanford University HIV Drug Resistance Database's algorithm (http://hivdb.stanford.edu). RESULTS: Among the 20 plasma samples, 13 got PCR products because of their VL values higher than 1000 copies/ml.Meanwhile, the 13 samples got 65 sequences by using 5 primers each. Polymorphisms in subtype H and circulating recombinant forms (CRFs) CRF10_CD sequences were identified. An overall prevalence of 30.8% (4/13) resistance to NNRTIs, 7.7% (1/13) to PI and no NRTIs mutations were found. The most frequent substitutions (4/13) in the RT region at positions P225H, K238S, V179D, K238T and a major position I54S in PR implied to a multiple drug-resistance. A71V or L10V only, respectively, substitution in PR was found in 3 samples, but no any worse with drug sensitivity. CONCLUSION: HIV-1 polymorphisms in subtype H and CRFs CRF10_CD sequences were identified circulating in Liaoning. A major mutation position I54S in PR implied that it would be the time to commence a higher level drug regimen.
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Resistência a Múltiplos Medicamentos/genética , Farmacorresistência Viral/genética , Infecções por HIV/virologia , HIV-1/genética , Fármacos Anti-HIV/farmacologia , China , Farmacorresistência Viral/efeitos dos fármacos , Genótipo , Infecções por HIV/tratamento farmacológico , Humanos , Mutação , RNA Viral/genéticaRESUMO
OBJECTIVE: Ventral anterior homeobox 2 (VAX2) gene is a key regulating factor for the development of the ventral region of the eye, and has recently attracted much attention from the cancer treatment field. Our study aimed to explore the effect of VAX2 on papillary thyroid carcinoma (PTC). METHODS: We determined the expression levels of VAX2 in PTC based on The Cancer Genome Atlas (TCGA) database. We then assessed the prognosis of patients with PTC, and analyzed the association between VAX2 expression and clinicopathological characteristics. Subsequently, we measured the biological functions of VAX2 in PTC using qRT-PCR, cell counting kit-8 (CCK-8) assay, colony formation assay, wound healing assay, transwell assays and western blot. RESULTS: VAX2 was up-regulated in PTC tissues when compared with normal thyroid tissues, and high expression level of VAX2 was positively correlated with poor prognosis. Furthermore, knockdown of VAX2 significantly inhibited the proliferation, migration and invasion of PTC cells. Importantly, through western blot analysis, we found that the expression of phosphorylated-(p) ERK and p-MEK in ERK signaling pathway showed a significant decrease after knockdown of VAX2. CONCLUSION: These findings suggest that VAX2 may be involved in the malignant progression of PTC, and hold significant potential as a therapeutic target for PTC.
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BACKGROUND: Eosinophilic inflammation of the airways is a key characteristic of asthma. A defect in eosinophil apoptosis might contribute to the chronic tissue eosinophilia associated with asthma. OBJECTIVE: Our purpose was to examine whether the occurrence of apoptotic eosinophils in induced sputum from asthmatic patients correlate with interleukin (IL)-5 and eotaxin. METHODS: Thirty stable and 30 exacerbated asthmatic patients were recruited. Twenty healthy subjects were enrolled as a control group. Induced sputum was obtained from asthmatic patients and from control subjects. The number of apoptotic eosinophils in sputum was assessed by flow cytometry. In sputum supernatant, eosinophil cationic protein (ECP) was measured by sensitive radioimmunoassay, and IL-5 and eotaxin by sandwich enzyme linked immunosorbant assay. RESULTS: Levels of eosinophils, apoptotic eosinophils, IL-5, ECP and eotaxin from asthmatic patients were higher than those from healthy subjects. Thirty exacerbated asthmatics showed higher proportions of eosinophils (median 29.3%, range 13.4%-40.9%), more detectable levels of IL-5 (50.44, 32.99-67.01 pg/ml) and eotaxin (644.6, 197.4-937.7 pg/ml) in their sputum than the patients with stable asthma (P<0.05). There were significant inverse correlations between the levels of sputum IL-5 and the proportion of sputum eosinophil apoptosis in patients with exacerbated and stable asthma (r=-0.85 and -0.79, P<0.01 and P<0.05, respectively). Also inverse correlations were found between the levels of eotaxin and the proportion of sputum eosinophil apoptosis in exacerbated (r=-0.85, P<0.01), or stable asthma (r=-0.69, P<0.05). Additional positive correlations between the levels of sputum IL-5 and eotaxin in either exacerbatated (r=0.93, P<0.01) or stable asthma (r=0.82, P<0.05) were observed. CONCLUSIONS: Apoptosis of eosinophils might be suppressed by proinflammatory cytokines and chemokines such as IL-5 and eotaxin leading to their accumulation in the lung. Stimulation of eosinophils in airway with IL-5 and eotaxin may play a crucial role in allergic inflammation.
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Asma/patologia , Quimiocinas CC/análise , Eosinófilos/patologia , Interleucina-5/análise , Escarro/citologia , Adolescente , Adulto , Idoso , Apoptose , Asma/imunologia , Asma/fisiopatologia , Biomarcadores/análise , Quimiocina CCL11 , Proteína Catiônica de Eosinófilo/análise , Feminino , Volume Expiratório Forçado , Humanos , Masculino , Fluxo Máximo Médio Expiratório , Pessoa de Meia-Idade , Manejo de Espécimes/métodos , Escarro/química , Escarro/imunologiaRESUMO
The purpose of this study was to evaluate left ventricular mechanical dyssynchrony (LVMD) in chronic heart failure (CHF) patients using two-dimensional speckle tracking imaging (2D-STI), and also to compare the usefulness of three patterns of myocardial deformation in mechanical dyssynchrony assessment. Furthermore, the relationships between left ventricular ejection fraction (LVEF), QRS duration (QRSd), and LVMD were explored. In total, 78 patients and 60 healthy individuals (group 3) were enrolled. The patients were classified into two subgroups: LVEF≤35% (group 1), 35%
Assuntos
Insuficiência Cardíaca/diagnóstico por imagem , Ventrículos do Coração/diagnóstico por imagem , Disfunção Ventricular Esquerda/diagnóstico por imagem , Adulto , Idoso , Estudos de Casos e Controles , Doença Crônica , Feminino , Insuficiência Cardíaca/complicações , Insuficiência Cardíaca/patologia , Insuficiência Cardíaca/fisiopatologia , Frequência Cardíaca , Ventrículos do Coração/patologia , Ventrículos do Coração/fisiopatologia , Humanos , Masculino , Pessoa de Meia-Idade , Volume Sistólico , Ultrassonografia , Disfunção Ventricular Esquerda/complicações , Disfunção Ventricular Esquerda/patologia , Disfunção Ventricular Esquerda/fisiopatologiaRESUMO
OBJECTIVE: Since the advent in 2004 of highly active antiretroviral therapy (HAART) in Liaoning, a dramatic improvement had been seen in the number of patients attaining undetectable viral loads (92/104), but the extent of mutation diversity on human immunodeficiency virus 1 (HIV-1) and the prevalence of drug resistance had remained elusive. This study aimed to analyze both HIV-1 mutation profiles and prevalence related to antiretroviral resistance following therapeutic failure. METHODS: A total of 104 blood samples circling Liaoning from HAART-treated between 2004 and 2008 were studied. Patients' CD(4)(+) T-cell count and viral load were determined. HIV-1 pol (PR and part of RT) gene fragments were amplified from patients' plasma by reverse transcriptase polymerase chain reaction (RT-PCR) and nest-PCR, subsequently sequenced and analyzed. RESULTS: CD(4)(+) T cell numbers and viral replication capacity were assessed. 88.4% (92/104) of the patients were successful after initial non-suppressive NRTI & NNRTI-based HAART regimens. Subjects on non-nucleoside reverse transcriptase inhibitor (NNRTI) regimens developed more (6/104) drug-resistance mutations than those on nucleoside reverse transcriptase inhibitor (NRTI) regimens did (5/104). No protease-inhibitor (PI) drug resistance mutations developed. The whole rate of drug resistance mutations was about 6.73%. Subjects developing NNRTI-resistance (NNRTI-R) seemed more likely to develop drug-resistant viremia than with NRTI-based HAART. CONCLUSION: This finding might have implications in which that the prevalence of drug-resistance mutations was low but remained risk of transmission in HIV-infected therapeutic failure. Meanwhile, data from the present study showed that there was a high frequency of primary mutations, which offered resistance to nrti and nnrti. Monitoring patients with treatment failure seems an important tool in helping the physicians to improve their treatment schedule and to carry out epidemiological surveillance programs.