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1.
Biosens Bioelectron ; 259: 116402, 2024 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-38788342

RESUMO

In this work, a high-performance conjugated microporous polymer (CMP) decorated with BiOBr (Tr(PhXOD)3-CMP/BiOBr) is synthesized to application in construction of ultrasensitive photoelectrochemical (PEC) biosensor for sensing miRNA-122, by firstly coupling with efficient clip toehold-mediated allosteric bicycle strand displacement (ABSD). Notably, the Tr(PhXOD)3-CMP/BiOBr not only owns self-enhanced D-A-D structure that extremely shortens migration distance of photo-generated electron, but also forms Z-type heterostructure for accelerating electron-hole separation, thereby significantly enhancing the photocurrent with 10-fold higher than commonly used methods. Meanwhile, the clip toehold-mediated ABSD based on ternary linkage structure transformation avoids the attrition of invading strand, endowing the conservation of high concentration for undergoing rapid reaction with high-efficiency DNA amplification, which dramatically improves reaction time and superior target conversion. The experimental results indicate that proposed PEC biosensor had a high sensitivity to miRNA-122 with a detection limit of 0.49 fM, which provides a newly organic/inorganic photosensitive nanomaterials and efficient DNA strand displacement in bioanalytical and early clinical disease diagnosis.


Assuntos
Técnicas Biossensoriais , Limite de Detecção , MicroRNAs , Polímeros , Técnicas Biossensoriais/métodos , Polímeros/química , MicroRNAs/análise , Técnicas Eletroquímicas/métodos , Humanos , DNA/química
2.
Front Plant Sci ; 15: 1367299, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38716337

RESUMO

Angelica dahurica is a kind of Chinese traditional herbs with economic and ornament value, widely distributed in China. Despite its significance, there have been limited comprehensive investigations on the genome of A. dahurica, particularly regarding mitochondrial genomes. To investigate the conversion between mitochondrial genome and chloroplast genome, a complete and circular mitochondrial genome was assembled using Oxford Nanopore Technologies (ONT) long reads. The mitochondrial genome of A. dahurica had a length of 228,315 base pairs (bp) with 45.06% GC content. The mitochondrial genome encodes 56 genes, including 34 protein-coding genes, 19 tRNA genes and 3 rRNA genes. Moreover, we discovered that 9 homologous large fragments between chloroplast genome and mitochondrial genome based on sequence similarity. This is the first report for A. dahurica mitochondrial genome, which could provide an insight for communication between plastid genome, and also give a reference genome for medicinal plants within the Angelica family.

3.
Nat Prod Res ; : 1-8, 2024 Apr 10.
Artigo em Inglês | MEDLINE | ID: mdl-38597194

RESUMO

Sixteen triterpenoid saponins were isolated from the roots of Bupleurum scorzonerifolium Willd., including a new triterpenoid saponin and new natural saponin that was characterised by NMR for the first time, along with 14 known triterpenoid saponins. The structures of the compounds were established by 1D and 2D NMR spectroscopy, HR-ESI-MS, and comparison with the literature. The cytotoxic activity of the compounds against 4T1 cells was determined using the CCK8 method. Compounds 9 and 6 showed the strongest cytotoxic activity with IC50 values of 2.75 ± 0.86 and 3.78 ± 0.50 µM, respectively. Compounds 2-5 and 8 showed potent cytotoxic activity. Compounds 14 and 16 showed moderate cytotoxicity.

4.
Chem Biodivers ; : e202400635, 2024 Apr 30.
Artigo em Inglês | MEDLINE | ID: mdl-38687253

RESUMO

The phytochemical investigation of the fruits of Cornus officinalis yielded a new phenolic acid derivative, neophenolic acid A (1), and a novel flavonoid glycoside, (2R)-naringenin-7-O-ß-(6''-galloyl-glucopyranoside) (2 a), along with six known flavonoid glycosides (2 b-7). Their structures were determined by 1D, 2D NMR and HRESIMS data. The absolute configuration of 1 was established by ECD analysis. Compounds 1- 7 were evaluated for their neuroprotective activities against corticosterone (CORT)-induced injury in PC-12 cells. Compounds 1, 2 a, 2 b, 5, and 6 exhibited neuroprotective activities against CORT-induced neurotoxicity in PC-12 cells. The underlying mechanism study suggested that compounds 1, 2 a, 2 b, 5, and 6 were able to attenuate CORT-induced apoptosis and damage, increase the levels of MMP and decrease Ca2+ inward flow in PC-12 cells.

5.
Fitoterapia ; 175: 105883, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38458497

RESUMO

Parkinson's disease (PD) is the second most common neurodegenerative disease in the world. As one of the major degradation pathways, autophagy plays a pivotal role in maintaining the effective turnover of proteins and damaged organelles in cells. Lewy bodies composed of α-synuclein (α-syn) abnormally aggregated in the substantia nigra are important pathological features of PD, and autophagy dysfunction is considered to be an important factor leading to abnormal aggregation of α-syn. Phenylpropionamides (PHS) in the seed of Cannabis sativa L. have a protective effect on neuroinflammation and antioxidant activity. However, the therapeutic role of PHS in PD is unclear. In this study, the seeds of Cannabis sativa L. were extracted under reflux with 60% EtOH-H2O, and the 60% EtOH-H2O elution fraction was identified as PHS with the UPLC-QTOF-MS. The 1-methyl-4-phenyl-1,2,3,6-tetrahydro-pyridine (MPTP)-induced PD model in C57BL/6 J mice was used for behavioral and pharmacodynamic experiments. Behavioral symptoms were improved, Nissl-stained and TH-positive neurons in the substantia nigra were significantly increased in PHS-treated MPTP-induced PD model mice. Compared with the model group, PHS treatment reduced the expression level of α-syn, and the expression of TH increased significantly by western blotting, compared with the model group, the PHS group suppressed Caspase 3 and Bax expression and promoted Bcl-2 expression and levels of p62 decreased significantly, the ratio of LC3-II/I and p-mTOR/mTOR in the PHS group had a downward trend, suggesting that the therapeutic effect of PHS on MPTP-induced PD model mice may be triggered by the regulation of autophagy.


Assuntos
Autofagia , Cannabis , Camundongos Endogâmicos C57BL , Fármacos Neuroprotetores , Sementes , Animais , Autofagia/efeitos dos fármacos , Camundongos , Sementes/química , Cannabis/química , Masculino , Fármacos Neuroprotetores/farmacologia , Fármacos Neuroprotetores/isolamento & purificação , Doença de Parkinson/tratamento farmacológico , Substância Negra/efeitos dos fármacos , Modelos Animais de Doenças , Serina-Treonina Quinases TOR/metabolismo
6.
Fitoterapia ; 175: 105902, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38492866

RESUMO

Seven new triterpenoids, named Adeterpenoids A-G (1-7) and eight known compounds (8-15), were isolated from 70% ethanol extract of the roots of Adenophora tetraphylla (Thub.) Fisch. The compounds from it were separated by column chromatography techniques such as silica gel, ODS, and preparative liquid chromatography. Their structures were clarified based on extensive spectral analysis (1D, 2D-NMR, HR-ESI-MS, IR, UV, and CD) and comparison with the literature. At the same time, all compounds were evaluated for their cytotoxic activity against the LN229 (human glioma cell line). The results showed that compounds 2, 5, 6, 13, and 14 had a significant inhibitory effect on LN229 cells.


Assuntos
Antineoplásicos Fitogênicos , Raízes de Plantas , Triterpenos , Raízes de Plantas/química , Triterpenos/isolamento & purificação , Triterpenos/farmacologia , Triterpenos/química , Estrutura Molecular , Linhagem Celular Tumoral , Humanos , Antineoplásicos Fitogênicos/farmacologia , Antineoplásicos Fitogênicos/isolamento & purificação , Compostos Fitoquímicos/farmacologia , Compostos Fitoquímicos/isolamento & purificação , China
7.
Huan Jing Ke Xue ; 45(3): 1539-1552, 2024 Mar 08.
Artigo em Chinês | MEDLINE | ID: mdl-38471868

RESUMO

The global occurrences of lake eutrophication have led to algal bloom and the subsequent algal decomposition, releasing high amounts of algae-derived dissolved organic matter (DOM) into the lake water. Algae-derived DOM could regulate the quantity and composition of DOM in lake water and further impact the biogeochemical cycles of multiple elements. In this study, the dynamic changes in the quantity and quality of DOM during algal decomposition under different eutrophic scenarios (e.g., from oligotrophication to severe eutrophication) were monitored, and the corresponding environmental effects (e.g., microbial responses and greenhouse gas emissions) caused by algal decomposition were further explored. The results showed that algal decomposition significantly increased the DOM levels, bioavailability, and intensities of fluorescent components in the water. The total DOM levels gradually decreased, whereas the average molecular weight increased along the decomposition process. Furthermore, unsaturated hydrocarbon and aliphatic compounds were preferentially utilized by microorganisms during algal decomposition, and some refractory molecules (e.g., lignin, condensed hydrocarbons, and tannin with high O/C values) were synchronously generated, as evidenced by the results from ultra-high-resolution mass spectrometry. The dominant bacterial species during algal decomposition shifted from Proteobacteria (46%) to Bacteroidetes (42%). In addition, algae addition resulted in 1.2-5 times the emissions of CO2 and CH4 from water, and the emission rates could be well predicted by the optical index of a254 in water. This study provides comprehensive perspectives for understanding the environmental behaviors of aquatic DOM and further paves the ways for the mitigation of lake eutrophication.


Assuntos
Matéria Orgânica Dissolvida , Lagos , Lagos/química , Espectrometria de Massas , Bactérias , Água/análise , Eutrofização , China
8.
Arthrosc Sports Med Rehabil ; 6(2): 100881, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38328534

RESUMO

Purpose: To (1) evaluate the clinical and radiographic outcomes of patients with primary anterior cruciate ligament reconstruction (ACLR) with type II posterior lateral meniscus root tear (PLMRT) repair and (2) identify whether increased anterior tibial subluxation of the lateral compartment (ATSLC) and steeper posterior tibial slope (PTS) are associated with sagittal lateral meniscal extrusion (LME). Methods: Patients who underwent primary anatomic ACLR with concomitant type II PLMRTs using the all-inside side-to-side repair technique between November 2014 and September 2020 were identified. To be included, patients must have had a minimum of 2 years follow-up. All patients, including those with ATSLC and PTS and sagittal and coronal LME, were retrospectively reviewed clinically and radiologically. The patients were divided into 2 subgroups according to the occurrence of sagittal LME. Results: Forty patients were included in this study with a mean follow-up of 44 months (range, 24-94 months). In general, the postoperative parameters, including grade of pivot shift, side-to-side difference, ATSLC, Lysholm score, and International Knee Documentation Committee (IKDC) score, were significantly improved compared with the preoperative ones. However, postoperative sagittal LME was detected to be significantly larger than the preoperative one. Minimal clinically important difference (MCID) analysis for postoperative outcomes showed that the rate of patients who achieved MCID thresholds was 100% for Lysholm, 95% for IKDC, 42.50% for coronal LME, 62.50% for sagittal LME, 40% for ATSLC, and 100% for side-to-side difference. Further comparisons, where patients were divided into 2 subgroups according to the occurrence of sagittal LME, showed significant differences in PTS, ATSLC, and coronal LME. Conclusions: Clinical outcomes after type II PLMRT repair with primary ACLR were significantly improved, except for LME, at the 2-year postoperative follow-up. After repair of type II PLMRT injuries, the presence of sagittal LME was associated with increased PTS and ATSLC. Level of Evidence: Level III, retrospective cohort study.

9.
Fitoterapia ; 174: 105874, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38417684

RESUMO

Five new sesquiterpenoids, dictamtrinorguaianols E and F (1-2), and dictameudesmnosides F, G, and H (3-5), along with seven known sesquiterpenoids (6-12) were isolated from Dictamnus dasycarpus Turcz. The structures of all new compounds were characterized by spectroscopic methods, including UV, IR, HR-ESI-MS, and 1D and 2D NMR. The In-vitro anti-proliferative activities of all the compounds against two human cancer cell lines (SW982 and A549) were evaluated by CCK-8 assay. Compounds 1 and 4 showed medium anti-proliferative activity against SW982 cells, with IC50 values of 3.49 ± 0.10 and 6.42 ± 1.23 µM, respectively. Additionally, compounds 2, 7, and 8 exhibited medium anti-proliferative activity against A549 cells, with IC50 values ranging from 0.80 ± 0.05 to 6.60 ± 0.46 µM.


Assuntos
Dictamnus , Sesquiterpenos , Humanos , Dictamnus/química , Estrutura Molecular , Linhagem Celular , Espectroscopia de Ressonância Magnética , Sesquiterpenos/farmacologia
10.
Nat Prod Res ; : 1-8, 2024 Jan 17.
Artigo em Inglês | MEDLINE | ID: mdl-38232058

RESUMO

Two new quinoline alkaloids (1-2) together with twenty-two known alkaloids (3-24) were isolated and identified from Dictamnus dasycarpus Turcz. Compounds 6-7, 9, 11, 15-16, 19 and 24 were isolated from D. dasycarpus for the first time. The structures of all compounds were characterised by spectroscopic methods (1D, 2D NMR and HRESIMS). The anti-proliferative activity was mediated by the arrest of three human cancer cell lines (SW982, HepG2 and A549) of all the compounds that were evaluated by CCK-8 assay.

11.
World J Gastrointest Oncol ; 16(1): 90-101, 2024 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-38292843

RESUMO

BACKGROUND: Surgical resection remains the primary treatment for hepatic malignancies, and intraoperative bleeding is associated with a significantly increased risk of death. Therefore, accurate prediction of intraoperative bleeding risk in patients with hepatic malignancies is essential to preventing bleeding in advance and providing safer and more effective treatment. AIM: To develop a predictive model for intraoperative bleeding in primary hepatic malignancy patients for improving surgical planning and outcomes. METHODS: The retrospective analysis enrolled patients diagnosed with primary hepatic malignancies who underwent surgery at the Hepatobiliary Surgery Department of the Fourth Hospital of Hebei Medical University between 2010 and 2020. Logistic regression analysis was performed to identify potential risk factors for intraoperative bleeding. A prediction model was developed using Python programming language, and its accuracy was evaluated using receiver operating characteristic (ROC) curve analysis. RESULTS: Among 406 primary liver cancer patients, 16.0% (65/406) suffered massive intraoperative bleeding. Logistic regression analysis identified four variables as associated with intraoperative bleeding in these patients: ascites [odds ratio (OR): 22.839; P < 0.05], history of alcohol consumption (OR: 2.950; P < 0.015), TNM staging (OR: 2.441; P < 0.001), and albumin-bilirubin score (OR: 2.361; P < 0.001). These variables were used to construct the prediction model. The 406 patients were randomly assigned to a training set (70%) and a prediction set (30%). The area under the ROC curve values for the model's ability to predict intraoperative bleeding were 0.844 in the training set and 0.80 in the prediction set. CONCLUSION: The developed and validated model predicts significant intraoperative blood loss in primary hepatic malignancies using four preoperative clinical factors by considering four preoperative clinical factors: ascites, history of alcohol consumption, TNM staging, and albumin-bilirubin score. Consequently, this model holds promise for enhancing individualised surgical planning.

12.
J Nat Med ; 78(1): 33-41, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-37658159

RESUMO

Six new naphthoquinones, euchronin A-F (1-6) and nine known naphthoquinones (7-15), were isolated from the roots of Arnebia euchroma (Royle) Johnst. The structures of the new compounds were confirmed by extensive spectroscopic analyses, including UV, IR, HR-ESI-MS, 1D and 2D NMR. In the present study, we estimated the anti-proliferative activities of these compounds with HaCaT cells. The results indicated that compounds 2 and 4 showed strong anti-proliferative activities at 25 µM, with relative viability at 38.83% and 68.44%, respectively.


Assuntos
Boraginaceae , Naftoquinonas , Naftoquinonas/farmacologia , Naftoquinonas/química , Extratos Vegetais/farmacologia , Extratos Vegetais/análise , Boraginaceae/química
13.
Nat Prod Res ; 38(6): 1007-1015, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-37165597

RESUMO

Two new compounds (1 and 2), along with thirty-one known compounds (3-33) were isolated from the fruits of Solanum xanthocarpum. The structure of isolates was elucidated by analysis of spectroscopic data and the physicochemical methods. Meanwhile, the anti-inflammatory activity of isolates was determined using LPS-induced RAW 264.7 cells. The results of anti-inflammatory assays indicated that most isolated compounds (3, 4, 6, 8-14, 17-20, and 30) possessed significant nitric oxide (NO) production inhibition in lipopolysaccharide (LPS)-induced RAW 264.7 cells with IC50 values ranging from 14.33 to 48.55 µM.


Assuntos
Solanum , Solanum/química , Frutas/química , Lipopolissacarídeos/farmacologia , Extratos Vegetais/química , Fenóis/farmacologia , Fenóis/análise , Anti-Inflamatórios/química
14.
Angew Chem Int Ed Engl ; 63(3): e202313142, 2024 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-37917045

RESUMO

Sodium dual-ion batteries (Na-DIBs) have attracted increasing attention due to their high operative voltages and low-cost raw materials. However, the practical applications of Na-DIBs are still hindered by the issues, such as low capacity and poor Coulombic efficiency, which is highly correlated with the compatibility between electrode and electrolyte but rarely investigated. Herein, fluoroethylene carbonate (FEC) is introduced into the electrolyte to regulate cation/anion solvation structure and the stability of cathode/anode-electrolyte interphase of Na-DIBs. The FEC modulates the environment of PF6 - solvation sheath and facilitates the interaction of PF6 - on graphite. In addition, the NaF-rich interphase caused by the preferential decomposition of FEC effectively inhibits side reactions and pulverization of anodes with the electrolyte. Consequently, Sb||graphite full cells in FEC-containing electrolyte achieve an improved capacity, cycling stability and Coulombic efficiency. This work elucidates the underlying mechanism of bifunctional FEC and provides an alternative strategy of building high-performance dual ion batteries.

15.
J Ethnopharmacol ; 318(Pt A): 116806, 2024 Jan 10.
Artigo em Inglês | MEDLINE | ID: mdl-37460028

RESUMO

ETHNOPHARMACOLOGICAL RELEVANCE: Diarrhea is a frequently encountered gastrointestinal complication in clinical practice, and E. coli is one of the main causative agents. Although Qingjie decoction (QJD) has been shown to be highly effective in treating diarrhea by eliminating heat-toxin, the underlying molecular mechanisms and pathways of QJD remain unclear. AIM OF REVIEW: The aim of this research was to explore the effects and fundamental mechanism of QJD on diarrhea induced by E.coli in rats. MATERIALS AND METHODS: Initially, we used UHPLC-MS/MS analysis to identify the chemical composition of QJD. Then, we constructed a visualization network using network pharmacology. Next, we utilized metabolomics to identify differentially expressed metabolites of QJD that are effective in treating diarrhea. RESULTS: The chemical composition of QJD was analyzed using UHPLC-MS/MS, which identified a total of 292 components. Using a network pharmacology approach, 127 bioactive compounds of QJD were screened, targeting 171 potential diarrhea treatment targets. TNF-α, IL-6, IL-1ß, and CAT were identified as important targets through visualizing the PPI network. Enrichment analysis demonstrated significant enrichment in the TNF signaling pathway, IL-17 signaling pathway, and PI3K-Akt signaling pathway. QJD showed beneficial effects, such as increased body weight, decreased fecal water content, and reduced inflammatory cell infiltration in the duodenum and colon, as well as maintaining the structure of the duodenum and colon. Metabolomic analysis revealed 32 differentially expressed metabolites in the control, model and QJD-H groups, including glucose, valine, and cysteine. Functional analysis indicated that differential metabolites were related to energy metabolism, including glucose metabolism, TCA cycle, and amino acid metabolism. CONCLUSION: QJD significantly increased body weight, decreased water content in feces, relieved inflammatory cell infiltration, maintained the structure of duodenum and colon. Combining network analysis and metabolomics, QJD exerted therapeutic effects by inhibiting inflammation and oxidative stress, regulating glucose metabolism, tricarboxylic acid metabolism, and amino acid metabolism.


Assuntos
Medicamentos de Ervas Chinesas , Animais , Ratos , Escherichia coli , Fosfatidilinositol 3-Quinases , Espectrometria de Massas em Tandem , Metabolômica , Metabolismo Energético , Diarreia/induzido quimicamente , Diarreia/tratamento farmacológico , Cisteína , Glucose , Inflamação , Peso Corporal , Medicamentos de Ervas Chinesas/farmacologia , Medicamentos de Ervas Chinesas/uso terapêutico
16.
Front Psychol ; 14: 1268091, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-38145000

RESUMO

This study examines the impact of ethical leadership on top management team (TMT) decision-making regarding corporate social responsibility (CSR), considering the mediating role of TMT passion and the moderating role of performance stress. The study distinguishes between TMT harmonious and obsessive work passion and categorizes CSR as proactive and reactive. The findings reveal the following: (1) Ethical leadership positively influences proactive CSR, with TMT harmonious work passion acting as a positive mediator and TMT obsessive work passion playing a negative mediating role; (2) ethical leadership positively affects reactive CSR, with both TMT harmonious and obsessive work passion serving as positive mediators; (3) performance stress diminishes the impact of ethical leadership on TMT harmonious work passion; however, it amplifies the effect on TMT obsessive work passion. Consequently, the mediating effect of TMT harmonious work passion weakens, while the mediating effect of TMT obsessive work passion strengthens. This study emphasizes the significant role of TMT in CSR strategic decision-making and proposes a novel mediating mechanism through which ethical leadership drives CSR decision-making by considering TMT work passion. These findings reconcile the theoretical-practical conflict and have important theoretical and practical implications for enterprises in fulfilling their social responsibility.

17.
Biomed Pharmacother ; 168: 115825, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-37924791

RESUMO

Alzheimer's disease (AD) is a progressive neurodegenerative disease for which there is a lack of effective therapeutic drugs. There is great potential for natural products to be used in the development of anti-AD drugs. P-coumaric acid (PCA), a small molecule phenolic acid widely distributed in the plant kingdom, has pharmacological effects such as neuroprotection, but its anti-AD mechanism has not been fully elucidated. In the current study, we investigated the mechanism of PCA intervention in the Aß25-35-induced AD model using gut microbiomics and serum metabolomics combined with in vitro and in vivo pharmacological experiments. PCA was found to ameliorate cognitive dysfunction and neuronal cell damage in Aß25-35-injected mice as measured by behavioral, pathological and biochemical indicators. 16S rDNA sequencing and serum metabolomics showed that PCA reduced the abundance of pro-inflammatory-associated microbiota (morganella, holdemanella, fusicatenibacter and serratia) in the gut, which were closely associated with metabolites of the glucose metabolism, arachidonic acid metabolism, tyrosine metabolism and phospholipid metabolism pathways in serum. Next, in vivo and in vitro pharmacological investigations revealed that PCA regulated Aß25-35-induced disruption of glucose metabolism through activation of PI3K/AKT/Glut1 signaling. Additionally, PCA ameliorated Aß25-35-induced neuroinflammation by inhibiting nuclear translocation of NF-κB and by modulating upstream MAPK signaling. In conclusion, PCA ameliorated cognitive deficits in Aß25-35-induced AD mice by regulating glucose metabolism and neuroinflammation, and the mechanism is related not only to restoring homeostasis of gut microbiota and serum metabolites, but also to PI3K/AKT/Glut1 and MAPK/NF-κB signaling.


Assuntos
Doença de Alzheimer , Microbioma Gastrointestinal , Doenças Neurodegenerativas , Camundongos , Animais , Peptídeos beta-Amiloides/metabolismo , Transportador de Glucose Tipo 1/metabolismo , NF-kappa B/metabolismo , Proteínas Proto-Oncogênicas c-akt/metabolismo , Fosfatidilinositol 3-Quinases/metabolismo , Doenças Neuroinflamatórias , Doenças Neurodegenerativas/patologia , Doença de Alzheimer/induzido quimicamente , Doença de Alzheimer/tratamento farmacológico , Doença de Alzheimer/metabolismo , Glucose/metabolismo , Encéfalo
18.
Bone Res ; 11(1): 56, 2023 10 26.
Artigo em Inglês | MEDLINE | ID: mdl-37884520

RESUMO

Despite the diverse roles of tripartite motif (Trim)-containing proteins in the regulation of autophagy, the innate immune response, and cell differentiation, their roles in skeletal diseases are largely unknown. We recently demonstrated that Trim21 plays a crucial role in regulating osteoblast (OB) differentiation in osteosarcoma. However, how Trim21 contributes to skeletal degenerative disorders, including osteoporosis, remains unknown. First, human and mouse bone specimens were evaluated, and the results showed that Trim21 expression was significantly elevated in bone tissues obtained from osteoporosis patients. Next, we found that global knockout of the Trim21 gene (KO, Trim21-/-) resulted in higher bone mass compared to that of the control littermates. We further demonstrated that loss of Trim21 promoted bone formation by enhancing the osteogenic differentiation of bone marrow mesenchymal stem cells (BMSCs) and elevating the activity of OBs; moreover, Trim21 depletion suppressed osteoclast (OC) formation of RAW264.7 cells. In addition, the differentiation of OCs from bone marrow-derived macrophages (BMMs) isolated from Trim21-/- and Ctsk-cre; Trim21f/f mice was largely compromised compared to that of the littermate control mice. Mechanistically, YAP1/ß-catenin signaling was identified and demonstrated to be required for the Trim21-mediated osteogenic differentiation of BMSCs. More importantly, the loss of Trim21 prevented ovariectomy (OVX)- and lipopolysaccharide (LPS)-induced bone loss in vivo by orchestrating the coupling of OBs and OCs through YAP1 signaling. Our current study demonstrated that Trim21 is crucial for regulating OB-mediated bone formation and OC-mediated bone resorption, thereby providing a basis for exploring Trim21 as a novel dual-targeting approach for treating osteoporosis and pathological bone loss.


Assuntos
Osteogênese , Osteoporose , Animais , Feminino , Humanos , Camundongos , beta Catenina/genética , Osso e Ossos/metabolismo , Diferenciação Celular/genética , Osteogênese/genética , Osteoporose/genética
19.
CMAJ Open ; 11(5): E1020-E1024, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37907215

RESUMO

BACKGROUND: Most antibiotics dispensed by community pharmacies in Canada are prescribed by family physicians, but using the prescribing information contained within primary care electronic medical records (EMRs) for secondary purposes can be challenging owing to variable data quality. We used antibiotic medications as an exemplar to validate a machine-learning approach for cleaning and coding medication data in a pan-Canadian primary care EMR database. METHODS: The Canadian Primary Care Sentinel Surveillance Network database contained an estimated 42 million medication records, which we mapped to an Anatomic Therapeutic Chemical (ATC) code by applying a semisupervised classification model developed using reference standard labels derived from the Health Canada Drug Product Database. We validated the resulting ATC codes in a subset of antibiotic records (16 119 unique strings) to determine whether the algorithm correctly classified the medication according to manual review of the original medication record. RESULTS: In the antibiotic subset, the algorithm showed high validity (sensitivity 99.5%, specificity 92.4%, positive predictive value 98.6%, negative predictive value 97.0%) in classifying whether the medication was an antibiotic. INTERPRETATION: Our machine-learning algorithm classified unstructured antibiotic medication data from primary care with a high degree of accuracy. Access to cleaned EMR data can support important secondary uses, including community-based antibiotic prescribing surveillance and practice improvement.

20.
Hum Vaccin Immunother ; 19(2): 2263228, 2023 08.
Artigo em Inglês | MEDLINE | ID: mdl-37843437

RESUMO

Rotavirus remains a major cause of diarrhea among 5-y-old children, and vaccination is currently the most effective and economical measure. We conducted a randomized, double-blind, placebo-controlled phase II clinical trial designed to determine the dosage, immunogenicity, and safety profile of a novel hexavalent rotavirus vaccine. In total, 480 eligible healthy infants, who were 6-12 weeks of age at the time of randomization were randomly allocated (1:1:1) to receive 105.5 focus-forming unit (FFU) or 106.5FFU of vaccine or placebo on a 0, 28 and 56-d schedule. Blood samples were collected 28 d after the third dose to assess rotavirus immunoglobulin A (IgA) antibody levels. Adverse events (AEs) up to 28 d after each dose and serious adverse events (SAEs) up to 6 months after the third dose were recorded as safety measurements. The anti-rotavirus IgA seroconversion rate of the vaccine groups reached more than 70.00%, ranging from 74.63% to 76.87%. The postdose 3 (PD3) geometric mean concentrations (GMCs) of anti-rotavirus IgA among vaccine recipients ranged from 76.97 U/ml to 84.46 U/ml. At least one solicited AE was recorded in 114 infants (71.25%) in the high-dose vaccine group, 106 infants (66.25%) in the low-dose vaccine group and 104 infants (65.00%) in the placebo group. The most frequently solicited AE was fever. The novel oral hexavalent rotavirus vaccine was safe and immunogenic in infants support the conclusion to advance the candidate vaccine for phase 3 efficacy trials.


Assuntos
Infecções por Rotavirus , Vacinas contra Rotavirus , Rotavirus , Humanos , Lactente , Anticorpos Antivirais , Método Duplo-Cego , População do Leste Asiático , Imunogenicidade da Vacina , Imunoglobulina A , Infecções por Rotavirus/prevenção & controle , Vacinas contra Rotavirus/efeitos adversos , Vacinas contra Rotavirus/uso terapêutico , Vacinas Atenuadas , Vacinas Combinadas
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