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1.
BMC Vet Res ; 20(1): 182, 2024 May 08.
Artigo em Inglês | MEDLINE | ID: mdl-38720329

RESUMO

BACKGROUND: Porcine cysticercosis, a serious zoonotic parasitic disease, is caused by the larvae of Taenia solium and has been acknowledged by the World Organization for Animal Health. The current detection methods of Cysticercus cellulosae cannot meet the needs of large-scale and rapid detection in the field. We hypothesized that the immunofluorescence chromatography test strip (ICS) for detecting Cysticercus cellulosae, according to optimization of a series of reaction systems was conducted, and sensitivity, specificity, and stability testing, and was finally compared with ELISA. This method utilizes Eu3+-labeled time-resolved fluorescent microspheres (TRFM) coupled with TSOL18 antigen to detect TSOL18 antibodies in infected pig sera. RESULTS: ICS and autopsy have highly consistent diagnostic results (n = 133), as determined by Cohen's κ analysis (κ = 0.925). And the results showed that the proposed ICS are high sensitivity (0.9459) with specificity (0.9792). The ICS was unable to detect positive samples of other parasites. It can be stored for at least six months at 4℃. CONCLUSIONS: In summary, we established a TRFM-ICS method with higher sensitivity and specificity than indirect ELISA. Results obtained from serum samples can be read within 10 min, indicating a rapid, user-friendly test suitable for large-scale field detection.


Assuntos
Anticorpos Anti-Helmínticos , Antígenos de Helmintos , Cisticercose , Ensaio de Imunoadsorção Enzimática , Imunofluorescência , Sensibilidade e Especificidade , Doenças dos Suínos , Animais , Suínos , Doenças dos Suínos/diagnóstico , Doenças dos Suínos/parasitologia , Doenças dos Suínos/sangue , Cisticercose/veterinária , Cisticercose/diagnóstico , Anticorpos Anti-Helmínticos/sangue , Antígenos de Helmintos/sangue , Antígenos de Helmintos/imunologia , Imunofluorescência/veterinária , Imunofluorescência/métodos , Ensaio de Imunoadsorção Enzimática/veterinária , Ensaio de Imunoadsorção Enzimática/métodos , Cysticercus/imunologia , Taenia solium/imunologia
2.
Heliyon ; 10(9): e30015, 2024 May 15.
Artigo em Inglês | MEDLINE | ID: mdl-38707411

RESUMO

Here, we presented 6 patients who were admitted to our institution and diagnosed as myasthenia gravis (MG) with tongue muscle atrophy. All these 6 patients developed symptoms of bulbar muscle weakness in acetylcholine receptor antibodies positive MG (AChR-MG) (3/6), muscle-specific receptor tyrosine kinase antibodies positive MG (MuSK-MG) (1/6), and sero-negative MG (2/6). Most of patients had "triple-furrowed" tongue except for patient 2 with irregular atrophy of tongue muscle. Tongue muscle atrophy occurs in patients with MuSK-MG, AChR-MG, and sero-negative MG. Atrophied tongue muscles of five patients with MG were reversible after immunotherapy.

3.
Front Physiol ; 15: 1343219, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38737829

RESUMO

Introduction: Exercise, health, and the gut microbiota (GM) are strongly correlated. Research indicates that professional athletes, especially ultra-marathon runners, have unique GM characteristics. However, more research has focused on elite athletes, with little attention given to amateur sports enthusiasts, especially those in the middle-aged population. Therefore, this study focuses on the impact of long-term running on the composition and potential functions of the GM in middle-aged individuals. Methods: We compared the GM of 25 middle-aged serious runnerswith 22 sedentary healthy controls who had minimal exercise habitsusing 16S rRNA gene sequencing. Additionally, we assessed dietary habits using a food frequency questionnaire. Results and Discussion: Statistical analysis indicates that there is no significant difference in dietary patterns between the control group and serious runners. Diversity analysis results indicate that there is no significant difference in α diversity between the two groups of GM, but there is a significant difference in ß diversity. Analysis of the composition of GM reveals that Ruminococcus and Coprococcus are significantly enriched in serious runners, whereas Bacteroides, Lachnoclostridium, and Lachnospira are enriched in the control group. Differential analysis of functional pathway prediction results reveals significant differences in the functional metabolism levels of GM between serious runners and the control group. Further correlation analysis results indicate that this difference may be closely related to variations in GM. In conclusion, our results suggest that long-term exercise can lead to changes in the composition of the GM. These changes have the potential to impact the overall health of the individual by influencing metabolic regulation.

4.
Appl Microbiol Biotechnol ; 108(1): 300, 2024 Apr 15.
Artigo em Inglês | MEDLINE | ID: mdl-38619710

RESUMO

The gut microbiota (GM) and its potential functions play a crucial role in maintaining host health and longevity. The aim of this study was to investigate the potential relationship between GM and longevity. We collected fecal samples from 92 healthy volunteers (middle-aged and elderly: 43-79 years old; longevity: ≥ 90 years old) from Changshou Town, Zhongxiang City, Hubei, China. In addition, we collected samples from 30 healthy middle-aged and elderly controls (aged 51-70 years) from Wuhan, Hubei. The 16S rDNA V3 + V4 region of the fecal samples was sequenced using high-throughput sequencing technology. Diversity analysis results showed that the elderly group with longevity and the elderly group with low body mass index (BMI) exhibited higher α diversity. However, no significant difference was observed in ß diversity. The results of the microbiome composition indicate that Firmicutes, Proteobacteria, and Bacteroidota are the core phyla in all groups. Compared to younger elderly individuals, Akkermansia and Lactobacillus are significantly enriched in the long-lived elderly group, while Megamonas is significantly reduced. In addition, a high abundance of Akkermansia is a significant characteristic of elderly populations with low BMI values. Furthermore, the functional prediction results showed that the elderly longevity group had higher abilities in short-chain fatty acid metabolism, amino acid metabolism, and xenobiotic biodegradation. Taken together, our study provides characteristic information on GM in the long-lived elderly population in Changshou Town. This study can serve as a valuable addition to the current research on age-related GM. KEY POINTS: • The gut microbiota of elderly individuals with longevity and low BMI exhibit higher alpha diversity • Gut microbiota diversity did not differ significantly between genders in the elderly population • Several potentially beneficial bacteria (e.g., Akkermansia and Lactobacillus) are enriched in long-lived individuals.


Assuntos
Microbioma Gastrointestinal , Microbiota , Pessoa de Meia-Idade , Humanos , Idoso , Feminino , Masculino , Adulto , Idoso de 80 Anos ou mais , China , Akkermansia , Bacteroidetes , Lactobacillus
5.
Gene ; 914: 148400, 2024 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-38527672

RESUMO

Slow transit constipation (STC) is a refractory gastrointestinal disease, accounting for approximately 13 âˆ¼ 37 % of chronic constipation. However, the molecular mechanism of STC remains poorly understood. Herein, this study aims to identify the key mRNAs and lncRNAs associated with STC. To this end, we performed high-throughput RNA sequencing to identify differentially expressed (DE) mRNAs and lncRNAs in the whole-layer sigmoid intestinal tissues from 4 STC patients and 4 non-STC patients. The identified DE lncRNAs and mRNAs were validated through quantitative real-time PCR. Weighted gene co-expression network analysis (WGCNA) and Pearson correlation analysis were conducted to determine the significantly correlated DE mRNA-lncRNA pairs. A total of 1420 DE lncRNAs and 1634 DE mRNAs were identified. Kyoto Encyclopedia of Genes and Genomes analysis of DE mRNAs indicated that these DE mRNAs might be associated with systemic lupus erythematosus, alcoholism, intestinal immune network for IgA production, inflammatory bowel disease, NF-kappa B signaling pathway. WGCNA and Pearson correlation analyses jointly identified 16,577 significantly correlated DE mRNA-lncRNA pairs. Furthermore, lncRNAs LINC00641, LINC02268, LINC03013 were identified as hub lncRNAs. The protein-protein interaction (PPI) network of proteins encoded by DE mRNAs was established, and PPI-based analysis revealed that Interleukin 2(IL2), CD80 molecule (CD80), interleukin-17A (IL-17A) might play significant roles in the development of STC. This study analyzes the expression profiles of lncRNAs and mRNAs associated with STC. Our findings will contribute to further understanding of the molecular mechanism of STC and provide potential diagnostic or therapeutic biomarkers for STC.


Assuntos
Constipação Intestinal , Perfilação da Expressão Gênica , Redes Reguladoras de Genes , RNA Longo não Codificante , RNA Mensageiro , Humanos , RNA Longo não Codificante/genética , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Constipação Intestinal/genética , Feminino , Perfilação da Expressão Gênica/métodos , Masculino , Mapas de Interação de Proteínas/genética , Pessoa de Meia-Idade , Adulto , Sequenciamento de Nucleotídeos em Larga Escala
6.
Heliyon ; 10(5): e26741, 2024 Mar 15.
Artigo em Inglês | MEDLINE | ID: mdl-38449651

RESUMO

Background: Monocytes play an essential role in developing autoimmune diseases; however, their association with myasthenia gravis (MG) development is unclear. Methods: We performed a two-sample Mendelian randomization analysis to assess the causal relationship between monocyte-associated traits and MG, reviewing summary statistics of genome-wide association studies (GWAS). Results: Using the inverse variance weighted method, the following were found to be causally associated with MG: HLA-DR on monocytes (OR, 1.363; 95% CI, 1.158-1.605; P = 2E-04), HLA-DR on CD14+ monocytes (OR, 1.324; 95% CI, 1.183-1.482; P = 1.08E-06), HLA-DR on CD14+CD16- monocytes (OR, 1.313; 95% CI, 1.177-1.465; P = 1.07E-06), CD40 on monocytes (OR, 1.135; 95% CI, 1.012-1.272; P < 0.05), CD40 on CD14+CD16- monocytes (OR, 1.142; 95% CI, 1.015-1.285; P < 0.05), CD40 on CD14+CD16+ monocytes (OR, 1.142; 95% CI, 1.021-1.278; P < 0.05), CD64 on CD14+CD16+ monocytes (OR, 1.286; 95% CI, 1.019-1.623; P < 0.05). Conclusions: The present study suggests a causal relationship between the upregulation of CD40, HLA-DR, and CD64 on monocytes and the development of MG. Altered monocyte function may potentially be a risk factor for MG and a therapeutic target.

7.
ACS Pharmacol Transl Sci ; 7(3): 743-756, 2024 Mar 08.
Artigo em Inglês | MEDLINE | ID: mdl-38481697

RESUMO

Aging poses obstacles to the functionality of human mesenchymal stem cells (MSCs), resulting in a notable decline in their valuable contribution to myocardial infarction (MI). MicroRNAs (miRNAs) play a pivotal role in governing MSC aging; nonetheless, the specific mechanisms remain puzzling. This research delved into the value of miR-873-5p in the management of MSC aging and investigated whether the restraint of miR-873-5p could regenerate aged MSCs (AMSCs), thereby enhancing their healing success for MI. In this study, MSCs were isolated from both young donors (referred to as YMSCs) and aged donors (referred to as AMSCs). The senescence status of these MSCs was evaluated through the application of age-related ß-galactosidase (SA-ß-gal) staining. Following this assessment, the MSCs, including those treated with anti-miR-873-5p-AMSCs, were then transplanted into the hearts of Sprague-Dawley rats experiencing acute myocardial infarction. Increasing miR-873-5p levels in YMSCs resulted in elevated cellular aging, whereas reducing miR-873-5p expression decreased aging in AMSCs. Mechanistically, miR-873-5p inhibited autophagy in MSCs through the AMPK signaling pathway, leading to cellular aging by suppressing the Cab39 expression. Partial alleviation of these effects was achieved by the administration of the autophagy inhibitor 3-methyladenine. Grafting of anti-miR-873-5p-AMSCs, by enhancing angiogenesis and bolstering cell survival, led to an improvement in cardiac function in the rat model, unlike the transplantation of AMSCs. miR-873-5p which serves as a pivotal element in mediating MSC aging through its regulation of the Cab39/AMPK signaling pathway. It represents an innovative target for revitalizing AMSCs and enhancing their heart-protective abilities.

9.
Artigo em Inglês | MEDLINE | ID: mdl-38401092

RESUMO

Objective: This study aimed to analyze the prognosis of patients with non-small cell lung cancer (NSCLC) after receiving immunotherapy and construct a prediction model to evaluate the overall survival rate of patients. Methods: This study was a retrospective study that collected data from 493 NSCLC patients who received immunotherapy for the first time. Survival data were analyzed using Cox regression models and the Kaplan-Meier method. The average age of patients was 56 years, and the data collection process included regular outpatient follow-up and observation of overall survival (OS) in the last 36 months. Results: Multivariate analysis identified significant risk factors such as smoking history, age, T stage, and M stage on survival and disease progression. The model's performance indicators (C-index and AUC) and calibration curve verified the model's accuracy and predictive ability. In the training set, the AUCs of 3-year and 5-year survival were 0.761 and 0.763, respectively, and in the validation set, they were 0.739 and 0.761. Conclusion: This study developed a prediction model for evaluating the survival of NSCLC patients after immunotherapy that integrates multiple influencing factors. This predictive model can be used as a tool to assess individual risks in NSCLC patients after immunotherapy, helping clinicians to develop more precise treatment and follow-up plans, potentially improving patient outcomes.

10.
Scand Stat Theory Appl ; 51(1): 334-354, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38370508

RESUMO

Practical problems with missing data are common, and many methods have been developed concerning the validity and/or efficiency of statistical procedures. On a central focus, there have been longstanding interests on the mechanism governing data missingness, and correctly deciding the appropriate mechanism is crucially relevant for conducting proper practical investigations. In this paper, we present a new hypothesis testing approach for deciding between the conventional notions of missing at random and missing not at random in generalized linear models in the presence of instrumental variables. The foundational idea is to develop appropriate discrepancy measures between estimators whose properties significantly differ only when missing at random does not hold. We show that our testing approach achieves an objective data-oriented choice between missing at random or not. We demonstrate the feasibility, validity, and efficacy of the new test by theoretical analysis, simulation studies, and a real data analysis.

11.
medRxiv ; 2024 Jan 10.
Artigo em Inglês | MEDLINE | ID: mdl-38260403

RESUMO

Genome-wide association studies (GWAS) have been instrumental in identifying genetic associations for various diseases and traits. However, uncovering genetic underpinnings among traits beyond univariate phenotype associations remains a challenge. Multi-phenotype associations (MPA), or genetic pleiotropy, offer important insights into shared genes and pathways among traits, enhancing our understanding of genetic architectures of complex diseases. GWAS of biobank-linked electronic health record (EHR) data are increasingly being utilized to identify MPA among various traits and diseases. However, methodologies that can efficiently take advantage of distributed EHR to detect MPA are still lacking. Here, we introduce mixWAS, a novel algorithm that efficiently and losslessly integrates multiple EHRs via summary statistics, allowing the detection of MPA among mixed phenotypes while accounting for heterogeneities across EHRs. Simulations demonstrate that mixWAS outperforms the widely used MPA detection method, Phenome-wide association study (PheWAS), across diverse scenarios. Applying mixWAS to data from seven EHRs in the US, we identified 4,534 MPA among blood lipids, BMI, and circulatory diseases. Validation in an independent EHR data from UK confirmed 97.7% of the associations. mixWAS fundamentally improves the detection of MPA and is available as a free, open-source software.

12.
Heliyon ; 10(1): e23745, 2024 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-38192761

RESUMO

Background: Myasthenia gravis (MG) is an autoimmune disease characterized by generalized skeletal muscle contraction weakness due to autoantibodies targeting neural-muscular junctions. Here, we investigated the relationship between key cytokines and MG type, disease course, antibodies, and comorbidities. Method: Cytokine levels in serum samples collected from MG (n = 45) and healthy control (HC, n = 38) patients from January 2020 to June 2022 were quantified via flow cytometry. Results: Levels of IL-6 were higher in the MG group versus healthy individuals (p = 0.026) and in patients with generalized versus ocular MG (p = 0.019). IL-6 levels were positively correlated with QMG score. In patients with MG with both AChR and Titin antibodies, serum levels of sFas and granulysin were higher than in those with AChR alone (p = 0.036, and p = 0.028, respectively). LOMG had a reduction in serum levels of IL-2 compared to EOMG (p = 0.036). LOMG patients with diabetes had lower serum levels of IL-2, IL-4, and IFN-γ (p = 0.044, p = 0.038, and p = 0.047, respectively) versus those without diabetes. sFas in the MG with Abnormal thymus were reduced compared to those in MG with Normal thymus (p = 0.008). Conclusions: This study revealed a positive correlation between IL-6 level and MG status. Serum cytokine levels of the AChR + Titin MG group differed from those of the AChR group. LOMG had a lower IL-2 level. Comorbidities affect some cytokines in peripheral blood in MG serum.

13.
Aging (Albany NY) ; 16(1): 299-321, 2024 Jan 04.
Artigo em Inglês | MEDLINE | ID: mdl-38180752

RESUMO

Ischemic stroke (IS) is one of the principal causes of disability and death worldwide. Berberine (BBR), derived from the traditional Chinese herbal medicine Huang Lian, has been reported to inhibit the progression of stroke, but the specific mechanism whereby BBR modulates the progression of ischemic stroke remains unclear. N6-methyladenosine (m6A) modification is the most typical epigenetic modification of mRNA post-transcriptional modifications, among which METTL3 is the most common methylation transferase. During the study, the middle cerebral artery occlusion/reperfusion (MCAO/R) was established in mice, and the mice primary astrocytes and neurons induced by oxygen-glucose deprivation/reoxygenation (OGD/R) was simulated in vitro. Level of LncNEAT1, miR-377-3p was detected via RT-qPCR. The levels of Nampt and METTL3 were measured by Western blot. CCK8 and LDH assay was performed to detect cell viability. Here, we found that berberine alleviates MCAO/R-induced ischemic injury and up-regulates the expression of Nampt in astrocytes, miR-377-3p inhibits the expression of Nampt in astrocytes after OGD/R, thus promoting neuronal injury. NEAT1 binds to miR-377-3p in OGD/R astrocytes and plays a neuronal protective role as a ceRNA. METTL3 can enhance NEAT1 stability in OGD/R astrocytes by modulating m6A modification of NEAT1. Taken together, our results demonstrate that berberine exerts neuroprotective effects via the m6A methyltransferase METTL3, which regulates the NEAT1/miR-377-3p/Nampt axis in mouse astrocytes to ameliorate cerebral ischemia/reperfusion (I/R) injury.


Assuntos
Berberina , AVC Isquêmico , MicroRNAs , Traumatismo por Reperfusão , Camundongos , Animais , AVC Isquêmico/metabolismo , Berberina/farmacologia , Berberina/uso terapêutico , Neuroproteção , Astrócitos/metabolismo , MicroRNAs/metabolismo , Infarto da Artéria Cerebral Média/tratamento farmacológico , Infarto da Artéria Cerebral Média/metabolismo , Traumatismo por Reperfusão/metabolismo , Metiltransferases/genética , Metiltransferases/metabolismo , Apoptose/genética , Glucose/metabolismo
14.
Mol Neurobiol ; 2024 Jan 17.
Artigo em Inglês | MEDLINE | ID: mdl-38233687

RESUMO

Perioperative neurocognitive impairment (PND) is a common medical complication in the postoperative period. General anesthesia through volatile anesthetics poses a high risk of POCD. Moreover, the developing brain is especially vulnerable to anesthesia-induced neurotoxicity. Therefore, finding a practical approach to prevent or alleviate neonatal isoflurane (ISO) exposure-induced brain injury and cognitive decline is essential for reducing medical complications following major surgery during the early postnatal period. Using a repeated neonatal ISO exposure-induced PND rat model, we investigated the effects of methylene blue (MB) pretreatment on repeated neonatal isoflurane exposure-induced brain injury and memory loss. Intraperitoneal injection of low-dose MB (1 mg/kg) was conducted three times 24 h before each ISO exposure. The Barnes maze and novel objection test were conducted to assess learning and memory. Immunofluorescence staining, F-Jade C staining, TUNEL staining, and Western blot analysis were performed to determine mitochondrial fragmentation, neuronal injury, degeneration, and apoptosis. Evans blue extravasation assay, total antioxidant capacity assay, MDA assay kit, and related inflammatory assay kits were used to test blood-brain barrier (BBB) disruption, antioxidant capacity, and neuroinflammation. Behavioral tests revealed that MB pretreatment significantly ameliorated ISO exposure-induced cognitive deficits. In addition, MB pretreatment alleviates neuronal injury, apoptosis, and degeneration. Furthermore, the BBB integrity was preserved by MB pretreatment. Additional studies revealed that ISO-induced excessive mitochondrial fragmentation, oxidative stress, and neuroinflammation were significantly attenuated by MB pretreatment in the PND rat model. Our findings suggest that MB pretreatment alleviates ISO exposure-induced brain injury and memory loss for the first time, supporting MB pretreatment as a promising approach to protect the brain against neonatal ISO exposure-induced postoperative cognitive dysfunction.

15.
Cells ; 13(2)2024 01 06.
Artigo em Inglês | MEDLINE | ID: mdl-38247805

RESUMO

Low-dose aspirin (LDA) is efficacious in preventing preeclampsia, but its mechanism of action is unclear. Conflicting evidence suggests that it may inhibit placental trophoblast release of soluble fms-like tyrosine kinase-1 (sFlt1), a key mediator of preeclampsia. We examined whether, and at what concentrations, aspirin and its principal metabolite, salicylic acid, modulate sFlt1 release and/or expression in trophoblasts. Human trophoblast lines BeWo and HTR-8/SVneo were cultured; BeWo cells were also treated with 1% oxygen vs. normoxia to mimic hypoxia in preeclamptic placentas. Cells were treated with aspirin or salicylic acid vs. vehicle for 24 h at concentrations relevant to LDA and at higher concentrations. Protein concentrations (ELISA) and mRNA expression (RT-PCR) of sFlt1 were determined. Under normoxia, LDA-relevant concentrations of aspirin (10-50 µmol/L) or salicylic acid (20-100 µmol/L) had no significant effect on sFlt1 protein release or mRNA expression in BeWo cells. However, inhibition was observed at higher concentrations (1 mmol/L for aspirin and ≥200 µmol/L for salicylic acid). Hypoxia enhanced sFlt1 protein release and mRNA expression in BeWo cells, but these responses were not significantly affected by either aspirin or salicylic acid at LDA concentrations. Similarly, neither drug altered sFlt1 protein secretion or mRNA expression in normoxic HTR-8/SVneo cells at LDA concentrations. We suggest that direct modulation of trophoblast release or expression of sFlt1 is unlikely to be a mechanism underlying the clinical efficacy of LDA in preeclampsia.


Assuntos
Aspirina , Pré-Eclâmpsia , Trofoblastos , Receptor 1 de Fatores de Crescimento do Endotélio Vascular , Feminino , Humanos , Gravidez , Aspirina/farmacologia , Hipóxia , Placenta , Pré-Eclâmpsia/tratamento farmacológico , Receptores Proteína Tirosina Quinases , RNA Mensageiro/genética , Ácido Salicílico/farmacologia , Trofoblastos/efeitos dos fármacos , Trofoblastos/metabolismo , Receptor 1 de Fatores de Crescimento do Endotélio Vascular/efeitos dos fármacos
16.
Mini Rev Med Chem ; 24(2): 139-158, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-36998128

RESUMO

AVE 0991, a non-peptide analogue of Angiotensin-(1-7) [Ang-(1-7)], is orally active and physiologically well tolerated. Several studies have demonstrated that AVE 0991 improves glucose and lipid metabolism, and contains anti-inflammatory, anti-apoptotic, anti-fibrosis, and anti-oxidant effects. Numerous preclinical studies have also reported that AVE 0991 appears to have beneficial effects on a variety of systemic diseases, including cardiovascular, liver, kidney, cancer, diabetes, and nervous system diseases. This study searched multiple literature databases, including PubMed, Web of Science, EMBASE, Google Scholar, Cochrane Library, and the ClinicalTrials.gov website from the establishment to October 2022, using AVE 0991 as a keyword. This literature search revealed that AVE 0991 could play different roles via various signaling pathways. However, the potential mechanisms of these effects need further elucidation. This review summarizes the benefits of AVE 0991 in several medical problems, including the COVID-19 pandemic. The paper also describes the underlying mechanisms of AVE 0991, giving in-depth insights and perspectives on the pharmaceutical value of AVE 0991 in drug discovery and development.


Assuntos
Imidazóis , Pandemias , Humanos , Imidazóis/farmacologia , Transdução de Sinais , Rim
17.
J Am Med Inform Assoc ; 31(4): 809-819, 2024 Apr 03.
Artigo em Inglês | MEDLINE | ID: mdl-38065694

RESUMO

OBJECTIVES: COVID-19, since its emergence in December 2019, has globally impacted research. Over 360 000 COVID-19-related manuscripts have been published on PubMed and preprint servers like medRxiv and bioRxiv, with preprints comprising about 15% of all manuscripts. Yet, the role and impact of preprints on COVID-19 research and evidence synthesis remain uncertain. MATERIALS AND METHODS: We propose a novel data-driven method for assigning weights to individual preprints in systematic reviews and meta-analyses. This weight termed the "confidence score" is obtained using the survival cure model, also known as the survival mixture model, which takes into account the time elapsed between posting and publication of a preprint, as well as metadata such as the number of first 2-week citations, sample size, and study type. RESULTS: Using 146 preprints on COVID-19 therapeutics posted from the beginning of the pandemic through April 30, 2021, we validated the confidence scores, showing an area under the curve of 0.95 (95% CI, 0.92-0.98). Through a use case on the effectiveness of hydroxychloroquine, we demonstrated how these scores can be incorporated practically into meta-analyses to properly weigh preprints. DISCUSSION: It is important to note that our method does not aim to replace existing measures of study quality but rather serves as a supplementary measure that overcomes some limitations of current approaches. CONCLUSION: Our proposed confidence score has the potential to improve systematic reviews of evidence related to COVID-19 and other clinical conditions by providing a data-driven approach to including unpublished manuscripts.


Assuntos
COVID-19 , Humanos , Revisões Sistemáticas como Assunto , Projetos de Pesquisa , PubMed , Pandemias
18.
J Asian Nat Prod Res ; 26(3): 313-319, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-37342029

RESUMO

Two new rare trachylobane euphoratones A-B (1-2), together with five known diterpenoids (compounds 3-7), were isolated from the aerial parts of Euphorbia atoto. Their structures were unambiguously elucidated through HRESIMS, 1D and 2D NMR spectral analysis. Compounds 1, 3, 4 and 7 showed weak anti-inflammatory activities (IC50 77.49 ± 6.34, 41.61 ± 14.49, 16.00 ± 1.71 and 33.41 ± 4.52 µM, respectively), compared to the positive control quercetin (IC50 15.23 ± 0.65 µM).


Assuntos
Diterpenos , Euphorbia , Estrutura Molecular , Euphorbia/química , Espectroscopia de Ressonância Magnética , Diterpenos/farmacologia , Diterpenos/química , Anti-Inflamatórios/farmacologia , Anti-Inflamatórios/química
19.
J Biophotonics ; 17(2): e202300343, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-37909411

RESUMO

Repeated closed head injury (rCHI) is one of the most common brain injuries. Although extensive studies have focused on how to treat rCHI-induced brain injury and reduce the possibility of developing memory deficits, the prevention of rCHI-induced anxiety has received little research attention. The current study was designed to assess the effects of photobiomodulation (PBM) therapy in preventing anxiety following rCHI. The rCHI disease model was constructed by administering three repeated closed-head injuries within an interval 5 days. 2-min daily PBM therapy using an 808 nm continuous wave laser at 350 mW/cm2 on the scalp was implemented for 20 days. We found that PBM significantly ameliorated rCHII-induced anxiety-like behaviors, neuronal apoptosis, neuronal injury, promotes astrocyte/microglial polarization to anti-inflammatory phenotype, preserves mitochondrial fusion-related protein MFN2, attenuates the elevated mitochondrial fission-related protein DRP1, and mitigates neuronal senescence. We concluded that PBM therapy possesses great potential in preventing anxiety following rCHI.


Assuntos
Traumatismos Cranianos Fechados , Terapia com Luz de Baixa Intensidade , Humanos , Apoptose , Neurônios , Ansiedade/etiologia , Ansiedade/prevenção & controle
20.
Oncol Lett ; 27(1): 26, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-38073769

RESUMO

In a recent reclassification, adenocarcinoma in situ has been redefined as a glandular precursor lesion (GPL), alongside adenomatous hyperplasia. This updated classification necessitates corresponding adaptations in clinical diagnostic and therapeutic protocols. Consequently, the present study aimed to construct and validate a nomogram utilizing computed tomography (CT) texture features to effectively discriminate between minimally invasive adenocarcinoma (MIA) and GPL within sub-centimeter pulmonary ground glass nodules (GGNs). To achieve this objective, the present study employed rigorous statistical methodologies, including the Mann-Whitney U test and binary logistic regression analysis, to identify distinguishing features and establish predictive models. Subsequently, the diagnostic performance of these models underwent evaluation through receiver operating characteristic (ROC) curves. The area under the curve (AUC) in ROC curves was compared using DeLong's test. Additionally, the nomogram was constructed using R software and its diagnostic performance was validated through calibration curves. Within both the training and validation datasets, the AUCs were observed to be 0.992 [95% confidence interval (CI): 0.980-1.000] and 0.975 (95% CI: 0.935-1.000), respectively. DeLong's test revealed significant disparities in the AUCs between the nomogram and single-parameter models (P<0.001). Furthermore, calibration curves demonstrated concordance between the training and validation datasets. In conclusion, the application of a CT texture-based nomogram model has demonstrated aptitude in differentiating between MIA and GPL within sub-centimeter GGNs. This model streamlines the identification of optimal surgical interventions and enhances the sphere of clinical decision-making and management.

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