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1.
PeerJ ; 12: e17205, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38646480

RESUMEN

Background: Sepsis can disrupt immune regulation and lead to acute respiratory distress syndrome (ARDS) frequently. Remazolam, a fast-acting hypnotic drug with superior qualities compared to other drugs, was investigated for its potential protective effects against sepsis-induced ARDS. Methods: Forty Sprague-Dawley rats were randomly divided into four groups, including the sepsis + saline group, sham operation + saline group, sham operation + remazolam group and the sepsis + remazolam group. Lung tissues of rats were extracted for HE staining to assess lung damage, and the wet weight to dry weight (W/D) ratio was calculated. The levels of proinflammatory factors, anti-inflammatory factors, CD4+ and CD8+ T cells in peripheral blood, MDA, MPO, and ATP in the lung tissue were measured by using ELISA. Western blotting was performed to determine the protein expression of HMGB1 in lung tissues. Results: In comparison to the sham operation + saline and sham operation + remazolam groups, the sepsis + saline group exhibited significantly higher values for W/D ratio, lung damage score, IL-1ß, IL-6, TNF-α, PCT, CRP, MDP and MPO, while exhibiting lower levels of CD4+ and CD8+ T lymphocytes, PaO2, PCO2, and ATP. The rats in the sepsis + saline group displayed ruptured alveolar walls and evident interstitial lung edema. However, the rats in the sepsis + remazolam group showed improved alveolar structure. Furthermore, the HMGB1 protein expression in the sepsis + remazolam group was lower than the sepsis + saline group. Conclusion: Remazolam can alleviate the inflammatory response in infected rats, thereby alleviating lung injury and improving immune function, which may be attributed to the reduction in HMGB1 protein expression.


Asunto(s)
Ratas Sprague-Dawley , Síndrome de Dificultad Respiratoria , Sepsis , Animales , Sepsis/complicaciones , Sepsis/inmunología , Sepsis/metabolismo , Síndrome de Dificultad Respiratoria/inmunología , Ratas , Masculino , Proteína HMGB1/metabolismo , Modelos Animales de Enfermedad , Pulmón/patología , Pulmón/efectos de los fármacos , Pulmón/inmunología , Pulmón/metabolismo
2.
Bioorg Chem ; 147: 107351, 2024 Apr 06.
Artículo en Inglés | MEDLINE | ID: mdl-38593530

RESUMEN

Eleven triterpenoid saponins, including five new compounds, which were named densiflorasides A - E (1 - 5), were isolated from aerial parts of Mussaenda densiflora (Rubiaceae). Their structures were elucidated based on spectroscopic and single-crystal X-ray diffraction analyses and chemical methods. All the isolated compounds and the aglycone heinsiagenin A were evaluated for their immunosuppressive and antiosteoclastogenic activities in vitro. Compounds 6 - 8 and heinsiagenin A inhibited osteoclastogenesis, with IC50 values ranging from 8.24 to 17.7 µM. Furthermore, compounds 3, 6 - 8, and heinsiagenin A significantly inhibited T-cell proliferation, with IC50 values ranging from 2.56 to 8.60 µM, and compounds 3 - 5 and 11 inhibited the proliferation of B lymphocytes, with IC50 values ranging from 1.29 to 8.49 µM. Further in vivo experiments indicated that heinsiagenin A could significantly attenuate IMQ-induced psoriasis and DSS-induced colitis in mice.

3.
J Leukoc Biol ; 2024 Mar 08.
Artículo en Inglés | MEDLINE | ID: mdl-38456763

RESUMEN

Immune evasion by cancer cells poses a significant challenge for natural killer (NK) cell-based immunotherapy. Pyroptosis, a newly discovered form of programmed cell death, has shown great potential for enhancing the antitumor immunity of NK cells. Consequently, targeting pyroptosis has become an attractive strategy for boosting NK cell activity against cancer. In this study, various assays were conducted, including NK cell cytotoxicity assays, flow cytometry, xenograft tumor models, real-time PCR, and ELISA to assess NK cell-mediated cell killing, as well as gene and protein expressions. The results indicated that Euphohelioscopin A (Eupho-A), a potential pyroptosis activator, enhances NK cell-mediated lysis of tumor cells, resulting in inhibiting tumor growth that could be reversed by NK cell depletion. Furthermore, we found that Eupho-A significantly enhanced IFN-γ production in NK cells and synergistically up-regulated GSDME with IFN-γ in cancer cells. Eupho-A also increased the cleavage of GSDME, promoting GZMB-induced pyroptosis, which could be reversed by GSDME knockdown and IFN-γ blockade. Overall, the findings suggested that Eupho-A enhanced NK cell-mediated killing of cancer cells by triggering pyroptosis, making Eupho-A a promising pyroptosis activator with great potential for using in NK cell-based cancer immunotherapy.

4.
Bioorg Chem ; 141: 106886, 2023 12.
Artículo en Inglés | MEDLINE | ID: mdl-37778191

RESUMEN

Extensive phytochemical investigation of the seeds of Tripterygium wilfordii led to the identification of 54 polyesterified dihydro-ß-agarofuran-type sesquiterpenoids, including 27 previously undescribed ones, named Tripwilin I-XXVII (1-27). Comprehensive spectroscopic and single-crystal X-ray diffraction analyses, along with electronic circular dichroism (ECD) calculations were used for the structural elucidation of the new compounds. Biological assay revealed that 37 compounds among the isolates exhibited significant inhibition against osteoclastogenesis induced by receptor activator of nuclear factor-κB ligand (RANKL) at 10 µM. Further investigation indicated that Triptogelin C-3 (54), with the most potent osteoclastogenesis inhibitory activity, regulated the osteoclast marker genes (MMP-9, c-Fos, CTSK, and TRAP) and proteins in a dose-dependent manner in vitro. Besides, celaforin D-1 (28), 1α,6ß,15-triacetoxy-8α,9α-dibenzoyloxy-2α-hydroxydihydro-ß-agarofuran (34), triptogelin A-2 (37), and chiapen D (49) showed moderate suppressive effects on the proliferation of T and B lymphocytes with IC50 values ranging between 8.1 ± 0.8 and 19.0 ± 0.9 µM.


Asunto(s)
Sesquiterpenos , Tripterygium , Tripterygium/química , Osteogénesis , Sesquiterpenos/farmacología , Sesquiterpenos/química , Semillas , Estructura Molecular
5.
Nat Commun ; 14(1): 1185, 2023 03 02.
Artículo en Inglés | MEDLINE | ID: mdl-36864027

RESUMEN

Bacteria-triggered sepsis is characterized by systemic, uncontrolled inflammation in affected individuals. Controlling the excessive production of pro-inflammatory cytokines and subsequent organ dysfunction in sepsis remains challenging. Here, we demonstrate that Spi2a upregulation in lipopolysaccharide (LPS)-stimulated bone marrow-derived macrophages reduces the production of pro-inflammatory cytokines and myocardial impairment. In addition, exposure to LPS upregulates the lysine acetyltransferase, KAT2B, to promote METTL14 protein stability through acetylation at K398, leading to the increased m6A methylation of Spi2a in macrophages. m6A-methylated Spi2a directly binds to IKKß to impair IKK complex formation and inactivate the NF-κB pathway. The loss of m6A methylation in macrophages aggravates cytokine production and myocardial damage in mice under septic conditions, whereas forced expression of Spi2a reverses this phenotype. In septic patients, the mRNA expression levels of the human orthologue SERPINA3 negatively correlates with those of the cytokines, TNF, IL-6, IL-1ß and IFNγ. Altogether, these findings suggest that m6A methylation of Spi2a negatively regulates macrophage activation in the context of sepsis.


Asunto(s)
Lipopolisacáridos , Sepsis , Animales , Humanos , Ratones , Citocinas , Inflamación , Lipopolisacáridos/toxicidad , Sepsis/complicaciones , Cardiopatías/etiología
6.
Ultrasonics ; 132: 106970, 2023 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-36898297

RESUMEN

Here, a physics-enhanced multi-frequency acoustic hologram deep neural network (PhysNet_MFAH) method is proposed for designing multi-frequency acoustic holograms, which is built by incorporating multiple physical models that represent the physical processes of acoustic waves propagation for a set of design frequencies into a deep neural network. It is demonstrated that one needs only to feed a set of frequency-specific target patterns into the network, the proposed PhysNet_MFAH method can automatically, accurately, and rapidly generate a high-quality multi-frequency acoustic hologram for holographic rendering of different target acoustic fields in the same or distinct regions of the target plane when driven at different frequencies. Remarkably, it is also demonstrated that the proposed PhysNet_MFAH method can achieve a higher quality of the reconstructed acoustic intensity fields than the existing optimization methods IASA and DS for designing multi-frequency acoustic holograms at a relatively fast-computational speed. Furthermore, the performance dependencies of the proposed PhysNet_MFAH method on different design parameters are established, which provide insight into the performance of the reconstructed acoustic intensity fields when subject to different design conditions of the proposed PhysNet_MFAH method. We believe that the proposed PhysNet_MFAH method can facilitate many potential applications of acoustic holograms, ranging from dynamic particle manipulation to volumetric display.

7.
J Thorac Dis ; 14(10): 4003-4011, 2022 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-36389297

RESUMEN

Background: The incidence of sepsis has been steadily increasing worldwide, and the heart is one of the target organs that can be easily damaged by sepsis. At present, antibiotics and organ function support are the main treatment options for sepsis and multiple system organ dysfunction, but are still under investigation. Methods: Fifty rats were randomly divided into the sham operation group, sepsis group, sivelestat sodium low-dose (L) group (administered with sivelestat sodium 1.6 mg/kg), sivelestat sodium middle-dose (M) group (administered with sivelestat sodium 4.8 mg/kg), and sivelestat sodium high-dose (H) group (administered with sivelestat sodium 10 mg/kg). Morphological changes of myocardial cells and the distribution of extracellular signal-regulated kinase (ERK)1/2 proteins were observed by light microscope. Serum troponin-T, creatine kinase isoenzyme MB, brain natriuretic peptide, interleukin (IL)-6, tumor necrosis factor-α, and IL-1ß levels and changes in cardiac function indicators were measured. The protein expressions of Bax, Bcl-2, and ERK1/2 were detected by Western blotting. Results: Compared with the sham operation group, the release of inflammatory factors in the sepsis group increased; the protein expressions of Bax, Bcl-2, and ERK1/2 increased; left ventricular systolic pressure (LVSP), left ventricular end-diastolic pressure (LVEDP), and maximum rate of LVP rise (+dp/dtmax) level decreased, whereas -dp/dtmax increased. In the sivelestat sodium groups, the release of inflammatory factors decreased; Bax expression decreased, whereas Bcl-2 and ERK1/2 protein expressions increased; LVSP, LVEDP, and +dp/dtmax increased, whereas -dp/dtmax decreased. In addition, all of these changes occurred in a dose-dependent manner. Conclusions: Sivelestat sodium can effectively lower the expressions of inflammatory factors and improve cardiac function. It can act on the ERK1/2 signaling pathway to exert its cardiomyocyte-protective effect, and the activation of this signaling pathway can offer potential treatment sites for septic myocarditis.

8.
Artículo en Inglés | MEDLINE | ID: mdl-35982998

RESUMEN

Objective: The aim of this study was to observe the efficacy and mechanism of Draba scabra in sepsis myocarditis. Methods: The efficacy and pathways of action of Draba scabra on septic myocarditis were evaluated by making a rat model of sepsis with appendix perforation, using Draba scabra for pharmacological intervention, and measuring serum inflammatory factors, cardiac function indexes and parameters, and P38 protein expression in each group of rats, respectively. Results: The inflammatory factor level, apoptotic index of cardiomyocytes, and P38-MARK protein were significantly higher, while the cardiac function index and hemodynamic index were significantly decreased in group B, while the opposite was true in group E. The treatment was also found to be dose-dependent. Conclusion: Draba scabra pretreatment effectively reduces the inflammatory response and improves hemodynamic indexes in septic rats. The mechanism may be via the P38-MARK pathway to protect the myocardium.

9.
Bioorg Chem ; 119: 105534, 2022 02.
Artículo en Inglés | MEDLINE | ID: mdl-34894576

RESUMEN

Fourteen previously undescribed diterpenoids, including an unusual diterpenoid (1) with a 9,10-seco-jatrophane skeleton, ten jatrophane-type diterpenoids (2-11), two lathyrane-type diterpenoids (12, 13), and an abietane-type diterpenoid (14), together with thirty-six known ones (15-50), were isolated from the whole plants of Euphorbia helioscopia L. The structures of the new isolates were characterized by spectroscopic methods, single-crystal X-ray diffraction analysis, and computational prediction of ECD and chemical shifts. Thirty-nine abundant diterpenoids were evaluated for their enhancement of NK cell-mediated killing of NSCLC cells. As a result, compounds 24, 33, and 41 were found to significantly enhance the killing activity of NK cells towards H1299-luci cells and A549-luci cells at the concentration of 2.5 µM.


Asunto(s)
Antineoplásicos Fitogénicos/farmacología , Diterpenos/farmacología , Euphorbia/química , Células Asesinas Naturales/metabolismo , Antineoplásicos Fitogénicos/química , Antineoplásicos Fitogénicos/aislamiento & purificación , Línea Celular Tumoral , Proliferación Celular/efectos de los fármacos , Supervivencia Celular/efectos de los fármacos , Diterpenos/química , Diterpenos/aislamiento & purificación , Relación Dosis-Respuesta a Droga , Ensayos de Selección de Medicamentos Antitumorales , Humanos , Estructura Molecular , Relación Estructura-Actividad
10.
Front Comput Neurosci ; 16: 1075294, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-36686199

RESUMEN

Deep learning has achieved enormous success in various computer tasks. The excellent performance depends heavily on adequate training datasets, however, it is difficult to obtain abundant samples in practical applications. Few-shot learning is proposed to address the data limitation problem in the training process, which can perform rapid learning with few samples by utilizing prior knowledge. In this paper, we focus on few-shot classification to conduct a survey about the recent methods. First, we elaborate on the definition of the few-shot classification problem. Then we propose a newly organized taxonomy, discuss the application scenarios in which each method is effective, and compare the pros and cons of different methods. We classify few-shot image classification methods from four perspectives: (i) Data augmentation, which contains sample-level and task-level data augmentation. (ii) Metric-based method, which analyzes both feature embedding and metric function. (iii) Optimization method, which is compared from the aspects of self-learning and mutual learning. (iv) Model-based method, which is discussed from the perspectives of memory-based, rapid adaptation and multi-task learning. Finally, we conduct the conclusion and prospect of this paper.

11.
Ann Palliat Med ; 10(11): 11910-11917, 2021 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-34872315

RESUMEN

BACKGROUND: Acute respiratory distress syndrome (ARDS) is one of the most organ dysfunctions in sepsis. Although the development of therapeutic strategies such as protective mechanical ventilation technology has improved the mortality of ARDS patients, there is currently no effective drug for reducing the associated mortality. Our study aims to investigate the efficacy, safety, and pharmacoeconomics of sivelestat sodium in patients with septic ARDS, for providing the basis on clinical use of this drug. METHODS: This was a retrospective study of 140 patients with septic ARDS. Clinical information including general conditions, mechanical ventilation time, drug cost parameters, and adverse reactions. The partial pressure of O2/fraction of inspired oxygen (PaO2/FiO2), acute physiology and chronic health evaluation score (APACHE II score) and sequential organ failure assessment (SOFA score) are for assessing the severity illness. To evaluate the efficacy of sivelestat sodium on septic ARDS patients by comparing length of mechanical ventilation and intensive care unit (ICU) hospitalization, cost of hospitalization and mortality between the two groups. RESULTS: There were no significant differences in the incidence of organ failure, biochemical data, blood gas analysis, acute physiology and chronic health evaluation (APACHE II score), and SOFA score between the two groups on the day of admission. The PaO2/FiO2, APACHE II score, and SOFA score of the sivelestat sodium group were significantly better than in the control group (P<0.05). The length of mechanical ventilation, length of ICU hospitalization, and cost of ICU hospitalization were all lower in the sivelestat sodium group (P<0.05). No adverse events were reported during the study period. CONCLUSIONS: Sivelestat sodium significantly improves the oxygenation in patients with septic ARDS, together with reducing mechanical ventilation, ICU hospitalization, and medical costs.


Asunto(s)
Economía Farmacéutica , Síndrome de Dificultad Respiratoria , Glicina/análogos & derivados , Humanos , Síndrome de Dificultad Respiratoria/tratamiento farmacológico , Estudios Retrospectivos , Sodio , Sulfonamidas
12.
ACS Chem Neurosci ; 12(23): 4416-4427, 2021 12 01.
Artículo en Inglés | MEDLINE | ID: mdl-34755509

RESUMEN

The discovery of new therapeutic agents for ischemic stroke remains an urgent need. Here, we identified a novel phenyl carboxylic acid derivative, n-pentyl 4-(3,4-dihydroxyphenyl)-4-oxobutanoate (PDPOB), with anti-ischemic activities. The in vitro anti-ischemic neuroprotective and anti-inflammatory capacities of PDPOB were investigated using neuronal cells suffering from oxygen-glucose deprivation/reperfusion (OGD/R) and microglial cells stimulated by lipopolysaccharide (LPS). PDPOB attenuated the OGD/R-evoked cellular damage of SH-SY5Y cells and primary cortical neurons in a concentration-dependent manner. Likewise, PDPOB displayed protective roles against OGD/R-evoked multiaspect neuronal deterioration in SH-SY5Y cells, as evidenced by alleviated mitochondrial dysfunction, oxidative stress, and apoptosis. A further study unveiled the accelerated phosphorylation of protein kinase B (AKT) by PDPOB treatment, while blockade of phosphoinositide 3-kinase (PI3K)/AKT signaling substantially diminished the neuroprotective capacities of PDPOB. Additionally, the PDPOB pretreatment dampened the LPS-evoked neuroinflammation in BV2 cells, characterized by the suppressed secretion of nitric oxide (NO) and proinflammatory cytokines, as well as normalized expression of nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2). Western blotting further revealed that PDPOB abated the overabundant phosphorylation of the extracellular signal-regulated kinase (ERK), c-Jun-N-terminal kinase (JNK), and p38 in LPS-exposed BV2 cells. The intravenous application of PDPOB (30 mg/kg, single dose) attenuated ipsilateral cerebral infarction in middle cerebral artery occlusion (MCAO) rats, accompanied by recovered neurological behaviors. Collectively, the above observations provided substantial evidence for the favorable properties and mechanistic explanations of PDPOB in the regulation of ischemia-associated neuronal injury and microglial inflammation, which may furnish ideas for the discovery of new therapeutic strategies against cerebral ischemia.


Asunto(s)
Isquemia Encefálica , Fármacos Neuroprotectores , Daño por Reperfusión , Animales , Apoptosis , Isquemia Encefálica/tratamiento farmacológico , Isquemia , Enfermedades Neuroinflamatorias , Fármacos Neuroprotectores/farmacología , Fosfatidilinositol 3-Quinasa/farmacología , Fosfatidilinositol 3-Quinasas/metabolismo , Proteínas Proto-Oncogénicas c-akt , Ratas , Daño por Reperfusión/tratamiento farmacológico , Transducción de Señal
13.
J Acoust Soc Am ; 149(4): 2312, 2021 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-33940859

RESUMEN

Acoustic holographic techniques are crucial in diverse applications, such as three-dimensional holographic display and particle manipulation. However, conventional methods for computer-generated acoustics holography rely heavily on iterative optimization algorithms, which are time-consuming and particularly hinder their capacity of generating a dynamic hologram in real time. Here, a deep learning approach based on U-Net is proposed to rapidly generate an acoustic hologram with optimal amplitude and phase maps. It is demonstrated that, after being trained with adequate data that are numerically synthesized by the pseudo-inverse method, the proposed deep learning approach can generate both amplitude and phase maps for new target images with an improved overall reconstruction quality. Remarkably, after the offline cost is compensated by a lower online cost for the proposed DL approach, the hologram generation speed is significantly accelerated by the proposed deep learning approach as compared with the pseudo-inverse method, especially for complicated or dynamic images. With the hierarchical feature learning capability and the fast online computational speed, the proposed deep learning approach can serve as a smart platform for rapidly generating complete maps of holograms for the sophisticated or dynamical target images, leading to the new possibility of real-time acoustic-hologram-based applications.

14.
J Autism Dev Disord ; 51(10): 3610-3623, 2021 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-33394241

RESUMEN

Many neurodevelopmental disorders (NDDs) share common learning and behavioural impairments, as well as features such as dysregulation of the oxytocin hormone. Here, we examined DNA methylation (DNAm) in the 1st intron of the oxytocin receptor gene, OXTR, in patients with autism spectrum (ASD), attention deficit and hyperactivity (ADHD) and obsessive compulsive (OCD) disorders. DNAm of OXTR was assessed for cohorts of ASD (blood), ADHD (saliva), OCD (saliva), which uncovered sex-specific DNAm differences compared to neurotypical, tissue-matched controls. Individuals with ASD or ADHD exhibiting extreme DNAm values had lower IQ and more social problems, respectively, than those with DNAm within normative ranges. This suggests that OXTR DNAm patterns are altered across NDDs and may be correlated with common clinical outcomes.


Asunto(s)
Trastorno por Déficit de Atención con Hiperactividad , Trastorno del Espectro Autista , Trastorno Obsesivo Compulsivo , Trastorno por Déficit de Atención con Hiperactividad/genética , Trastorno del Espectro Autista/genética , Metilación de ADN , Femenino , Humanos , Masculino , Oxitocina/metabolismo , Receptores de Oxitocina/genética
15.
Neurochem Res ; 46(3): 686-698, 2021 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-33389470

RESUMEN

28-O-caffeoyl betulin (B-CA) has been demonstrated to reduce the cerebral infarct volume caused by transient middle cerebral artery occlusion (MCAO) injury. B-CA is a novel derivative of naturally occurring caffeoyl triterpene with little information associated with its pharmacological target(s). To date no data is available regarding the effect of B-CA on brain metabolism. In the present study, a 1H-NMR-based metabolomics approach was applied to investigate the therapeutic effects of B-CA on brain metabolism following MCAO in rats. Global metabolic profiles of the cortex in acute period (9 h after focal ischemia onset) after MCAO were compared between the groups (sham; MCAO + vehicle; MCAO + B-CA). MCAO induced several changes in the ipsilateral cortex of ischemic rats, which consequently led to the neuronal damage featured with the downregulation of NAA, including energy metabolism dysfunctions, oxidative stress, and neurotransmitter metabolism. Treatment with B-CA showed statistically significant rescue effects on the ischemic cortex of MCAO rats. Specifically, treatment with B-CA ameliorated the energy metabolism dysfunctions (back-regulating the levels of succinate, lactate, BCAAs, and carnitine), oxidative stress (upregulating the level of glutathione), and neurotransmitter metabolism disturbances (back-regulating the levels of γ-aminobutyric acid and acetylcholine) associated with the progression of ischemic stroke. With the administration of B-CA, the levels of three phospholipid related metabolites (O-phosphocholine, O-phosphoethanolamine, sn-glycero-3-phosphocholine) and NAA improved significantly. Overall, our findings suggest that treatment with B-CA may provide neuroprotection by augmenting the metabolic changes observed in the cortex following MCAO in rats.


Asunto(s)
Corteza Cerebral/metabolismo , Infarto de la Arteria Cerebral Media/metabolismo , Enfermedades Metabólicas/metabolismo , Metaboloma/efectos de los fármacos , Fármacos Neuroprotectores/uso terapéutico , Triterpenos/uso terapéutico , Animales , Corteza Cerebral/efectos de los fármacos , Infarto de la Arteria Cerebral Media/tratamiento farmacológico , Masculino , Enfermedades Metabólicas/tratamiento farmacológico , Metabolómica , Espectroscopía de Protones por Resonancia Magnética , Curva ROC , Ratas Sprague-Dawley
17.
BMJ Open ; 7(10): e017737, 2017 Oct 06.
Artículo en Inglés | MEDLINE | ID: mdl-28988181

RESUMEN

OBJECTIVES: We audited a selection of systematic reviews published in 2013 and reported on the proportion of reviews that researched for unpublished data, included unpublished data in analysis and assessed for publication bias. DESIGN: Audit of systematic reviews. DATA SOURCES: We searched PubMed and Ovid MEDLINE In-Process & Other Non-Indexed Citations between 1 January 2013 and 31 December 2013 for the following journals: Journal of the American Medical Association, The British Medical Journal, Lancet, Annals of Internal Medicine and the Cochrane Database of Systematic Reviews. We also searched the Cochrane Library and included 100 randomly selected Cochrane reviews. ELIGIBILITY CRITERIA: Systematic reviews published in 2013 in the selected journals were included. Methodological reviews were excluded. DATA EXTRACTION AND SYNTHESIS: Two reviewers independently reviewed each included systematic review. The following data were extracted: whether the review searched for grey literature or unpublished data, the sources searched, whether unpublished data were included in analysis, whether publication bias was assessed and whether there was evidence of publication bias. MAIN FINDINGS: 203 reviews were included for analysis. 36% (73/203) of studies did not describe any attempt to obtain unpublished studies or to search grey literature. 89% (116/130) of studies that sought unpublished data found them. 33% (68/203) of studies included an assessment of publication bias, and 40% (27/68) of these found evidence of publication bias. CONCLUSION: A significant fraction of systematic reviews included in our study did not search for unpublished data. Publication bias may be present in almost half the published systematic reviews that assessed for it. Exclusion of unpublished data may lead to biased estimates of efficacy or safety in systematic reviews.


Asunto(s)
Bibliometría , Recolección de Datos/normas , Sesgo de Publicación , Proyectos de Investigación/normas , Literatura de Revisión como Asunto , Humanos
19.
PLoS One ; 12(1): e0167609, 2017.
Artículo en Inglés | MEDLINE | ID: mdl-28052111

RESUMEN

OBJECTIVES: We report information about an unpublished 1970s study ("8-way" Bendectin Study) that aimed to evaluate the relative therapeutic efficacy of doxylamine, pyridoxine, and dicyclomine in the management of nausea and vomiting during pregnancy. We are publishing the trial's findings according to the restoring invisible and abandoned trials (RIAT) initiative because the trial was never published. DESIGN: Double blinded, multi-centred, randomized placebo-controlled study. SETTING: 14 clinics in the United States. PARTICIPANTS: 2308 patients in the first 12 weeks of pregnancy with complaints of nausea or vomiting were enrolled. INTERVENTIONS: Each patient was randomized to one of eight arms: placebo, doxylamine/pyridoxine/dicylcomine, doxylamine/pyridoxine, dicylomine/pyridoxine, doxylamine, dicyclomine/pyridoxine, pyridoxine and dicyclomine. Each patient was instructed to take 2 tablets at bedtime and 1 additional tablet in the afternoon or morning if needed, for 7 nights. OUTCOMES: Reported outcomes included the number of hours of nausea reported by patients, the frequency of vomiting reported by patients and the overall efficacy of medication as judged by physicians. RESULTS: Data from 1599 (69% of those randomized) participants were analyzed. Based on the available summary data of physician evaluation of symptoms and ignoring missing data and data integrity issues, the proportion of participants who were "evaluated moderate or excellent" was greater in each of the seven active treatment groups when compared with placebo (57%): doxylamine/pyridoxine/dicylcomine (14% absolute difference versus placebo; 95% CI: 4 to 24), doxylamine/pyridoxine (21; 95% CI 11 to 30), dicylomine/pyridoxine (21; 95% CI 11 to 30), doxylamine (20; 95% CI 10 to 29), dicyclomine/pyridoxine (4; 95% CI -6 to 14), pyridoxine (9; 95% CI -1 to 19) and dicyclomine (4; 95% CI -6 to 14). Based on incomplete information, the most common adverse events were apparently drowsiness and fatigue. There is a high risk of bias in these previously unpublished results given the high attrition rate in a 7 day trial, the lack of prespecified outcomes or analyses, and the exclusion of some data because of questionable data integrity. CONCLUSION: The available information about this "8-way Bendectin" trial indicates it should not be used to support the efficacy of doxylamine, pyridoxine or dicyclomine for the treatment of nausea and vomiting during pregnancy because of a high risk of bias. TRIAL REGISTRATION: Not registered.


Asunto(s)
Diciclomina/uso terapéutico , Doxilamina/uso terapéutico , Náusea/complicaciones , Náusea/tratamiento farmacológico , Complicaciones del Embarazo/tratamiento farmacológico , Publicaciones , Piridoxina/uso terapéutico , Vómitos/complicaciones , Vómitos/tratamiento farmacológico , Conducta Cooperativa , Diciclomina/efectos adversos , Doxilamina/efectos adversos , Combinación de Medicamentos , Femenino , Humanos , Médicos , Placebos , Embarazo , Sesgo de Publicación , Piridoxina/efectos adversos , Informe de Investigación , Riesgo
20.
J Nat Prod ; 79(12): 3039-3046, 2016 Dec 23.
Artículo en Inglés | MEDLINE | ID: mdl-28006915

RESUMEN

Seventeen ß-dihydroagarofuran-type sesquiterpenes were isolated from the seeds of Celastrus monospermus, and, among them, 15 (1-15) were identified as new natural products. Nine isolates were evaluated for their lifespan-extending effect using the standard model animal nematode Caenorhabditis elegans. As a result, all of the tested compounds prolonged the lifespan of C. elegans when compared to the blank control group (p < 0.0001). Among them, celaspermin E (5) extended the average lifespan and maximum lifespan of C. elegans, with effects similar to those of rapamycin, a positive control that has been found experimentally to delay the aging process of yeasts, worms, fruit flies, and mice.


Asunto(s)
Caenorhabditis elegans/efectos de los fármacos , Celastrus/química , Semillas/química , Sesquiterpenos/aislamiento & purificación , Sesquiterpenos/farmacología , Animales , Longevidad/efectos de los fármacos , Estructura Molecular , Sesquiterpenos/química
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