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1.
Ann Med Surg (Lond) ; 86(5): 2507-2517, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38694292

RESUMO

Background: Surgical excision is considered one of the most effective treatments for secondary osteosarcoma (SO). It remains unclear whether the survival of patients with secondary osteosarcoma (SO) could be associated with their surgical willingness. Materials and methods: The statistics of the patients diagnosed with SO between 1975 and 2008 were gathered from the surveillance epidemiology and end results (SEER) database. The patients were divided into three subgroups according to their surgical compliance. The authors used the multivariable Logistic regression analysis and cox regression method to reveal the influence of surgical compliance on prognosis and the risk factors of surgical compliance. Additionally, the authors formulated a nomogram model to predict the overall survival (OS) of patients. The concordance index (C-index) was used to evaluate the accuracy and practicability of the above prediction model. Results: Sixty-three (9.2%) of the 688 patients with SO who were recommended for surgical treatment refused to undergo surgery. Lower surgical compliance can be ascribed to an earlier time of diagnosis and refusal of chemotherapy. The lower overall survival (OS) {[hazard ratio (HR)] 1.733, [CI] 1.205-2.494, P value [P]=0.003} of not surgical compliant patients was verified by the multivariate cox regression method, compared with surgical compliant patients. In addition, the discernibility of the nomogram model was proven to be relatively high (C-index=0.748), by which we can calibrate 3-year- and 5-year OS prediction plots to obtain good concordance to the actual situation. Conclusions: Surgical compliance was proved to be an independent prognostic factor in the survival of patients with SO.

2.
Phytochem Anal ; 2024 Apr 19.
Artigo em Inglês | MEDLINE | ID: mdl-38639073

RESUMO

INTRODUCTION: The active constituents in Aurantii Fructus sourced from different regions within Hunan Province exhibit variations, with certain samples demonstrating substandard quality. OBJECTIVES: The aim of this study is to conduct a comparative analysis of the chemical composition and quality of Aurantii Fructus from various sources, establish a robust methodology for quality evaluation, and determine the optimal harvesting period. MATERIALS AND METHODS: The components of Aurantii Fructus were qualitatively analyzed using a non-targeted metabolomics approach. Multivariate statistical analyses were conducted to identify potential markers, enabling qualitative and quantitative evaluation of the quality and optimal harvest period of Aurantii Fructus. RESULTS: Overall, 155 compounds were identified in Aurantii Fructus, with Huangpi exhibiting the highest number of components. Eleven potential markers were selected to assess the quality of Aurantii Fructus. The average content of Huangpi was the highest, indicating a high level of similarity. The samples' overall scores were ordered as follows: Huangpi > Xiangcheng > Choucheng > Daidai. Anren and Changde's Huangpi exhibited high contents, being rich in chemical components, resulting in favorable scores. Similarly, Changde's Xiangcheng displayed significant medicinal value. As the harvest time was delayed, there was an increase in fruit size, accompanied by thinner peels and a continuous decrease in the contents of potential markers. The best harvest period of Aurantii Fructus was within 1 week before and after the Lesser Heat. CONCLUSION: The present study establishes a precise and efficient method for evaluating the quality of Aurantii Fructus, thereby providing more comprehensive insights into its composition. This research lays the foundation for subsequent development and utilization of Aurantii Fructus.

3.
Neurobiol Stress ; 30: 100624, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38524250

RESUMO

Gestational stress can exacerbate postpartum depression (PPD), for which treatment options remain limited. Environmental enrichment (EE) may be a therapeutic intervention for neuropsychiatric disorders, including depression, but the specific mechanisms by which EE might impact PPD remain unknown. Here we examined the behavioral, molecular, and cellular impact of EE in a stable PPD model in rats developed through maternal separation (MS). Maternal rats subjected to MS developed depression-like behavior and cognitive dysfunction together with evidence of significant neuroinflammation including microglia activation, neuronal apoptosis, and impaired synaptic plasticity. Expanding the duration of EE to throughout pregnancy and lactation, we observed an EE-associated reversal of MS-induced depressive phenotypes, inhibition of neuroinflammation and neuronal apoptosis, and improvement in synaptic plasticity in maternal rats. Thus, EE effectively alleviates neuroinflammation, neuronal apoptosis, damage to synaptic plasticity, and consequent depression-like behavior in mother rats experiencing MS-induced PPD, paving the way for new preventive and therapeutic strategies for PPD.

4.
Neuroimage Clin ; 41: 103581, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38430800

RESUMO

Arterial spin labeling (ASL) can be used to detect differences in perfusion for multiple brain regions thought to be important in major depressive disorder (MDD). However, the potential of cerebral blood flow (CBF) to predict MDD and its correlations between the blood lipid levels and immune markers, which are closely related to MDD and brain function change, remain unclear. The 451 individuals - 298 with MDD and 133 healthy controls who underwent MRI at a single time point with arterial spin labelling and a high resolution T1-weighted structural scan. A proportion of MDD also provided blood samples for analysis of lipid and immune markers. We performed CBF case-control comparisons, random forest model construction, and exploratory correlation analyses. Moreover, we investigated the relationship between gray matter volume (GMV), blood lipids, and the immune system within the same sample to assess the differences in CBF and GMV. We found that the left inferior parietal but supramarginal and angular gyrus were significantly different between the MDD patients and HCs (voxel-wise P < 0.001, cluster-wise FWE correction). And bilateral inferior temporal (ITG), right middle temporal gyrus and left precentral gyrus CBF predict MDD (the area under the receiver operating characteristic curve of the random forest model is 0.717) and that CBF is a more sensitive predictor of MDD than GMV. The left ITG showed a positive correlation trend with immunoglobulin G (r = 0.260) and CD4 counts (r = 0.283). The right ITG showed a correlation trend with Total Cholesterol (r = -0.249) and tumour necrosis factor-alpha (r = -0.295). Immunity and lipids were closely related to CBF change, with the immunity relationship potentially playing a greater role. The interactions between CBF, plasma lipids and immune index could therefore represent an MDD pathophysiological mechanism. The current findings provide evidence for targeted regulation of CBF or immune properties in MDD.


Assuntos
Transtorno Depressivo Maior , Substância Cinzenta , Humanos , Substância Cinzenta/diagnóstico por imagem , Substância Cinzenta/patologia , Transtorno Depressivo Maior/diagnóstico por imagem , Transtorno Depressivo Maior/patologia , Depressão , Encéfalo/patologia , Imageamento por Ressonância Magnética , Circulação Cerebrovascular/fisiologia , Marcadores de Spin , Biomarcadores , Lipídeos
5.
United European Gastroenterol J ; 12(3): 374-389, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38315582

RESUMO

AIMS: To investigate the current situation of mental psychology and quality of life (QoL) in patients with inflammatory bowel disease (IBD) in China, and analyze the influencing factors. METHODS: A unified questionnaire was developed to collect clinical data on IBD patients from 42 hospitals in 22 provinces from September 2021 to May 2022. Multivariate Logistic regression analysis was conducted, and independent influencing factors were screened out to construct nomogram. The consistency index (C-index), receiver operating characteristic (ROC) curve, area under the ROC curve (AUC), calibration curve, and decision curve analysis (DCA) were used to evaluate the discrimination, accuracy, and clinical utility of the nomogram model. RESULTS: A total of 2478 IBD patients were surveyed, including 1371 patients with ulcerative colitis (UC) and 1107 patients with Crohn's disease (CD). Among them, 25.5%, 29.7%, 60.2%, and 37.7% of IBD patients had anxiety, depression, sleep disturbance and poor QoL, respectively. The proportion of anxiety, depression, and poor QoL in UC patients was significantly higher than that in CD patients (all p < 0.05), but there was no difference in sleep disturbance between them (p = 0.737). Female, higher disease activity and the first visit were independent risk factors for anxiety, depression and sleep disturbance in IBD patients (all p < 0.05). The first visit, higher disease activity, abdominal pain and diarrhea symptoms, anxiety, depression and sleep disturbance were independent risk factors for the poor QoL of patients (all p < 0.05). The AUC value of the nomogram prediction model for predicting poor QoL was 0.773 (95% CI: 0.754-0.792). The calibration diagram of the model showed that the calibration curve fit well with the ideal curve, and DCA showed that the nomogram model could bring clinical benefits. CONCLUSION: IBD patients have higher anxiety, depression, and sleep disturbance, which affect their QoL. The nomogram prediction model we constructed has high accuracy and performance when predicting QoL.


Assuntos
Colite Ulcerativa , Doença de Crohn , Doenças Inflamatórias Intestinais , Transtornos do Sono-Vigília , Feminino , Humanos , China/epidemiologia , Colite Ulcerativa/diagnóstico , Colite Ulcerativa/epidemiologia , Colite Ulcerativa/psicologia , Doença de Crohn/diagnóstico , Doença de Crohn/epidemiologia , Doença de Crohn/psicologia , Doenças Inflamatórias Intestinais/epidemiologia , Doenças Inflamatórias Intestinais/psicologia , Qualidade de Vida , Transtornos do Sono-Vigília/epidemiologia , Transtornos do Sono-Vigília/etiologia , Transtornos do Sono-Vigília/diagnóstico , Masculino
6.
Neuroscience ; 542: 1-10, 2024 Mar 26.
Artigo em Inglês | MEDLINE | ID: mdl-38342336

RESUMO

Many central nervous system diseases are closely related to nerve damage caused by dysregulation of the endogenous neurotransmitter glutamate. Exosomes derived from bone marrow mesenchymal stem cells (BMSC-Exos) play an important role in improving injury and regeneration functions. However, its mechanism remains unknown. Therefore, the aim of this study is to investigate whether and how BMSC-Exos improve neurotoxicity caused by glutamate and to fill the gap in the literature. In this study, glutamate-treated HT22 cells were first exposed to mouse-derived BMSC-Exos at different concentrations to observe their effects on HT22 apoptosis. Next, we treated glutamate-treated HT22 cells with mouse-derived BMSC-Exos. We then inhibited the PI3K/Akt/mTOR signaling pathways using the PI3K/Akt inhibitor and the mTOR inhibitor, respectively, and observed the protective effect of mouse-derived BMSC-Exos on HT22 cells treated with glutamate. Our results show that BMSC-Exos reduced apoptosis triggered by glutamate stimulation, increased cell vitality, and decreased the levels of proapoptotic proteins while increasing the levels of anti-apoptotic proteins. The protective effect of BMSC-Exos was weakened when PI3K/Akt inhibitor and mTOR inhibitor were added. To sum up, we draw the following conclusions: BMSC-Exos can reduce neuronal apoptosis and apoptosis-related protein expression after glutamate stimulation by regulating the PI3K/Akt/mTOR signaling pathway.


Assuntos
Exossomos , MicroRNAs , Fármacos Neuroprotetores , Camundongos , Animais , Proteínas Proto-Oncogênicas c-akt/metabolismo , Fosfatidilinositol 3-Quinases/metabolismo , Ácido Glutâmico/toxicidade , Ácido Glutâmico/metabolismo , Fármacos Neuroprotetores/farmacologia , Fármacos Neuroprotetores/metabolismo , Exossomos/metabolismo , Serina-Treonina Quinases TOR/metabolismo , MicroRNAs/metabolismo
7.
Curr Med Chem ; 2024 Jan 03.
Artigo em Inglês | MEDLINE | ID: mdl-38310390

RESUMO

AIM: In this report, we performed a comprehensive analysis of data in colorectal cancer (CRC), to elucidate the association among Solute Carrier Family 4 Member 4 (SLC4A4) and the abundance of immunological features and immune cell infiltration in CRC, and to explore the impact of SLC4A4 on the CRC tumor microenvironment. BACKGROUND: Colorectal cancer (CRC) cases with advanced or distal metastases experience a survival rate of less than 20%, with the lack of spectral therapeutic targets and prognostic markers posing a significant challenge for CRC treatment. SLC4A4 may be a CRC-targeted therapy for which there is currently inadequate evidence Objective: To deeply and systematically reveal the characteristics of the tumor microenvironment created by SLC4A4. METHODS: We downloaded RNA sequencing files (TCGA-COADREAD), clinical data for Colon Cancer (COAD) and Rectal Cancer (READ) from the Cancer Genome Atlas. We evaluated the spearman correlation of SLC4A4 with immune features, Tracking Tumor Immunophenotype (TIP) score, and immune checkpoint gene expression. SLC4A4/immunity-related differentially expressed genes (DEGs) were identified in SLC4A4 expression groups and immune groups, and an assessment system for predicting CRC prognosis was constructed based on univariate COX and multivariate COX analyses. Based on the prognostic factors in CRC, we also constructed a nomogram to assess the survival risk status of CRC. Besides, we evaluated the potential association of SLC4A4 to immunotherapy. RESULTS: We found that SLC4A4 expression trended positively with immune checkpoint expression (PD-L1, CTLA4) and promoted infiltration of 27 immune cells. SLC4A4 promoted the infiltration of CD8 T cells, Dendritic cells, Macrophage, NK cells, and Th1 cells in CRC, shaping the inflammatory tumor microenvironment. Up-regulation of SLC4A4 expression might promote drug response to Anti-FGFR3_therapy, Anti-PPARG_therapy, Nivolumab, Ipilimumab in CRC patients, and down-regulation of SLC4A4 expression might promote drug response to Anti-EGFR_therapy, Aflibercept drug response. Based on the SLC4A4/immunization-related DEGs, we constructed RiskScore to assess the prognosis of CRC, which showed excellent predictive effect and robustness. RiskScore showed a trend of negative correlation with SLC4A4, which was consistent with the trend of the effect of SLC4A4 on CRC survival. Besides, RiskScore could also be useful for predicting patient prognosis. Finally, we constructed a nomogram for predicting CRC survival based on metrics with independent prognostic value (Age, M stage, Stage, RiskScore), which showed potential clinical value. CONCLUSION: Overall, upregulation of SLC4A4 expression promoted an inflammatory tumor microenvironment in CRC, and RiskScore predicted therapeutic expectancy. SLC4A4 could be a potentially clinically valuable target for CRC therapy.

8.
Chin J Integr Med ; 30(4): 299-310, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38212502

RESUMO

OBJECTIVE: To investigate the effect of isorhamnetin on the pathology of rheumatoid arthritis (RA). METHODS: Tumor necrosis factor (TNF)- α -induced fibroblast-like synoviocytes (FLS) was exposed to additional isorhamnetin (10, 20 and 40 µ mol/L). Overexpression vectors for matrix metalloproteinase-2 (MMP2) or MMP9 or SRC were transfected to explore their roles in isorhamnetin-mediated RA-FLS function. RA-FLS viability, migration, and invasion were evaluated. Moreover, a collagen-induced arthritis (CIA) rat model was established. Rats were randomly divided to sham, CIA, low-, medium-, and high-dosage groups using a random number table (n=5 in each group) and administed with normal saline or additional isorhamnetin [2, 10, and 20 mg/(kg·day)] for 4 weeks, respectively. Arthritis index was calculated and synovial tissue inflammation was determined in CIA rats. The levels of MMP2, MMP9, TNF-α, interleukin-6 (IL-6), and IL-1 ß, as well as the phosphorylation levels of SRC, extracellular regulated kinase (ERK), and cyclic adenosine monophosphate response element-binding (CREB), were detected in RA-FLS and synovial tissue. Molecular docking was also used to analyze the binding of isorhamnetin to SRC. RESULTS: In in vitro studies, isorhamnetin inhibited RA-FLS viability, migration and invasion (P<0.05). Isorhamnetin downregulated the levels of MMP2, MMP9, TNF-α, IL-6, and IL-1 ß in RA-FLS (P<0.05). The overexpression of either MMP2 or MMP9 reversed isorhamnetin-inhibited RA-FLS migration and invasion, as well as the levels of TNF-α, IL-6, and IL-1 ß (P<0.05). Furthermore, isorhamnetin bound to SRC and reduced the phosphorylation of SRC, ERK, and CREB (P<0.05). SRC overexpression reversed the inhibitory effect of isorhamnetin on RA-FLS viability, migration and invasion, as well as the negative regulation of MMP2 and MMP9 (P<0.05). In in vivo studies, isorhamnetin decreased arthritis index scores (P<0.05) and alleviated synovial inflammation. Isorhamnetin reduced the levels of MMP2, MMP9, TNF-α, IL-6, and IL-1 ß, as well as the phosphorylation of SRC, ERK, and CREB in synovial tissue (P<0.05). Notably, the inhibitory effect of isorhamnetin was more pronounced at higher concentrations (P<0.05). CONCLUSION: Isorhamnetin exhibited anti-RA effects through modulating SRC/ERK/CREB and MMP2/MMP9 signaling pathways, suggesting that isorhamnetin may be a potential therapeutic agent for RA.


Assuntos
Artrite Experimental , Artrite Reumatoide , Quercetina/análogos & derivados , Ratos , Animais , Metaloproteinase 2 da Matriz/metabolismo , Quinases da Família src/metabolismo , Quinases da Família src/farmacologia , Quinases da Família src/uso terapêutico , Interleucina-1beta/metabolismo , Interleucina-6/metabolismo , Fator de Necrose Tumoral alfa/metabolismo , Metaloproteinase 9 da Matriz/metabolismo , Simulação de Acoplamento Molecular , Artrite Reumatoide/tratamento farmacológico , Artrite Reumatoide/patologia , Membrana Sinovial/metabolismo , Membrana Sinovial/patologia , Inflamação/patologia , Artrite Experimental/tratamento farmacológico , Artrite Experimental/patologia , Células Cultivadas , Fibroblastos , Proliferação de Células
9.
Artigo em Inglês | MEDLINE | ID: mdl-38204249

RESUMO

AIMS AND OBJECTIVE: This study aimed to identify the bioactive compounds and explore the multi-target mechanisms of Salvia miltiorrhiza Bunge (SMB) against coronary heart disease (CHD) using an integrated serum pharmacochemistry and network pharmacology approach. MATERIALS AND METHODS: The chemical constituents of SMB were characterized by UPLC-MS. The absorbed ingredients and metabolites after oral SMB administration were identified in rat serum. Therapeutic targets of SMB against CHD were predicted by intersecting the targets of absorbed compounds from databases and CHD-associated genes. Protein-protein interaction network, pathway analysis, molecular docking, and molecular dynamic simulation were performed. RESULTS: A total of 61 SMB-derived compounds were identified in rat serum. Network analysis revealed 111 candidate targets highly related to CHD pathways. Further topological analysis identified 10 hub targets and 20 key active compounds, constructing an informative compoundtarget- pathway network. PTGS2 and TNF were predicted as primary targets of SMB against CHD based on molecular dynamic simulation. CONCLUSION: This integrated approach identified bioactive compounds and multi-target mechanisms of SMB against CHD. The results provide scientific evidence supporting SMB's clinical efficacy and reveal potential anti-CHD targets.

10.
Br J Clin Pharmacol ; 90(2): 452-462, 2024 02.
Artigo em Inglês | MEDLINE | ID: mdl-37749762

RESUMO

AIMS: This study aims to establish a population pharmacokinetic (PK) model of teicoplanin in Chinese adult patients to evaluate the dosing regimen in the label sheet and optimize it. METHODS: Nonlinear mixed-effects modelling was used to estimate PK parameters. Monte Carlo simulations were used to evaluate the attainment of various dosing regimens in achieving the target trough concentrations in patients with normal or decreased renal function. RESULTS: A total of 115 patients were enrolled in this retrospective study. Creatinine clearance (CrCL) and albumin (ALB) were identified as covariates on the clearance of teicoplanin. For the treatment of non-complicated methicillin-resistant Staphylococcus aureus (MRSA) infections in patients with normal renal function and serum ALB concentration, the recommended dosing regimen was 600 mg q12h with five administrations as the loading dose followed by 600 mg qd as the maintenance dose; for the treatment of serious and/or complicated MRSA infections, the recommended dosing regimen was 800 mg q12h with five administrations as the loading dose followed by 800 mg qd as the maintenance dose. It is worth noting that both the loading and maintenance doses ought to be modified based on the patient's renal function and serum ALB concentration. In addition, trough concentrations of teicoplanin were significantly increased every other week. CONCLUSIONS: Both loading dosing and maintenance dosing regimens were recommended to be adjusted according to patient's renal function and serum ALB concentration. In addition, it is necessary to perform follow-up therapeutic drug monitoring of teicoplanin at least once every week.


Assuntos
Staphylococcus aureus Resistente à Meticilina , Infecções Estafilocócicas , Adulto , Humanos , Teicoplanina/uso terapêutico , Antibacterianos , Estudos Retrospectivos , Monitoramento de Medicamentos , Albumina Sérica , Infecções Estafilocócicas/tratamento farmacológico
11.
J Gene Med ; 26(1): e3630, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-37985959

RESUMO

BACKGROUND: Cholangiocarcinoma (CCA) stands as an aggressive malignancy of the biliary tract. The interplay between the tumor and immune system plays a pivotal role in disease progression and treatment outcomes. Hence, the present study aimed to extensively explore the immunogenomic landscape of CCA, with the objective of unveiling unique molecular and immunological signatures that could guide personalized therapeutic approaches. METHODS: The study collected data from The Cancer Genome Atlas databases, performed gene set variation analysis for the chemokine ligand 5 (CCL5) high/low expression group, conducted principal component analysis, gene set enrichment analysis enrichment and mutation pattern analysis, generated a heatmap, and performed cox regression analysis. RESULTS: The two discrete subpopulations were found to exhibit contrasting mutational and immunogenomic characteristics, emphasizing the heterogeneity of CCA. These subsets also showed pronounced discrepancies in the infiltration of immune cells, indicating diverse interactions with the tumor immune microenvironment. Furthermore, the dissimilarities in mutational patterns were observed within the two CCA subgroups, with PBRM1 and BAP1 emerging as the most frequently mutated genes. In addition, a prognostic framework was formulated and validated utilizing the expression profiles of COX16 and RSAD2 genes, effectively segregating patients into high-risk and low-risk cohorts. Furthermore, the connections between immune-related parameters and these risk groups were identified, underscoring the potential significance of the immune microenvironment in patient prognosis. In vitro experiments have shown that COX16 promotes the proliferation and metastasis of CCA cells, whereas RSAD2 inhibits it. CONCLUSIONS: The present study provides an intricate depiction of the immunogenomic landscape of CCA based on CCL5 expression, thereby paving the way for novel immunotherapy strategies and prognostic assessment.


Assuntos
Neoplasias dos Ductos Biliares , Colangiocarcinoma , Humanos , Prognóstico , Ligantes , Neoplasias dos Ductos Biliares/genética , Neoplasias dos Ductos Biliares/terapia , Colangiocarcinoma/genética , Colangiocarcinoma/terapia , Colangiocarcinoma/patologia , Ductos Biliares Intra-Hepáticos/patologia , Microambiente Tumoral/genética , Quimiocina CCL5/genética
12.
Biol Psychiatry ; 2023 Dec 22.
Artigo em Inglês | MEDLINE | ID: mdl-38142718

RESUMO

BACKGROUND: Many metabolomics studies of depression have been performed, but these have been limited by their scale. A comprehensive in silico analysis of global metabolite levels in large populations could provide robust insights into the pathological mechanisms underlying depression and candidate clinical biomarkers. METHODS: Depression-associated metabolomics was studied in 2 datasets from the UK Biobank database: participants with lifetime depression (N = 123,459) and participants with current depression (N = 94,921). The Whitehall II cohort (N = 4744) was used for external validation. CatBoost machine learning was used for modeling, and Shapley additive explanations were used to interpret the model. Fivefold cross-validation was used to validate model performance, training the model on 3 of the 5 sets with the remaining 2 sets for validation and testing, respectively. Diagnostic performance was assessed using the area under the receiver operating characteristic curve. RESULTS: In the lifetime depression and current depression datasets and sex-specific analyses, 24 significantly associated metabolic biomarkers were identified, 12 of which overlapped in the 2 datasets. The addition of metabolic features slightly improved the performance of a diagnostic model using traditional (nonmetabolomics) risk factors alone (lifetime depression: area under the curve 0.655 vs. 0.658 with metabolomics; current depression: area under the curve 0.711 vs. 0.716 with metabolomics). CONCLUSIONS: The machine learning model identified 24 metabolic biomarkers associated with depression. If validated, metabolic biomarkers may have future clinical applications as supplementary information to guide early and population-based depression detection.

13.
bioRxiv ; 2023 Dec 08.
Artigo em Inglês | MEDLINE | ID: mdl-38106021

RESUMO

As in origami, morphogenesis in living systems heavily relies on tissue curving and folding, through the interplay between biochemical and biomechanical cues. In contrast, certain organs maintain their flat posture over several days. Here we identified a pathway, which is required for the maintenance of organ flatness, taking the sepal, the outermost floral organ, in Arabidopsis as a model system. Through genetic, cellular and mechanical approaches, our results demonstrate that global gene expression regulator VERNALIZATION INDEPENDENCE 4 (VIP4) fine-tunes the mechanical properties of sepal cell walls and maintains balanced growth on both sides of the sepals, mainly by orchestrating the distribution pattern of AUXIN RESPONSE FACTOR 3 (ARF3). vip4 mutation results in softer cell walls and faster cell growth on the adaxial sepal side, which eventually cause sepals to bend outward. Downstream of VIP4, ARF3 works through modulating auxin signaling to down-regulate pectin methylesterase VANGUARD1, resulting in decreased cell wall stiffness. Our work unravels a 3-component module, which relates hormonal patterns to organ curvature, and actively maintains sepal flatness during its growth.

14.
Zhongguo Zhong Yao Za Zhi ; 48(21): 5690-5700, 2023 Nov.
Artigo em Chinês | MEDLINE | ID: mdl-38114165

RESUMO

Rheumatoid arthritis(RA), as a chronic autoimmune disease, has a high incidence and disability rate, causing significant suffering to patients. Due to its complex pathogenesis, it has not been fully elucidated to date, and its treatment remains a challenging problem in the medical field. Although western medicine treatment options have certain efficacy, they require prolonged use and are expensive. Additionally, they carry risks of multiple infections and adverse reactions like malignancies. The Chinese herbal medicine Rhododendron molle is commonly used in folk medicine for its properties of dispelling wind, removing dampness, calming nerves, and alleviating pain in the treatment of diseases like rheumatic bone diseases. In recent years, modern clinical and pharmacological studies have shown that the diterpenoids in R. molle are effective components, exhibiting immune-regulatory, anti-inflammatory, and analgesic effects. This makes it a promising candidate for treating RA with a broad range of potential applications. However, R. molle has certain toxic properties that hinder its clinical application and lead to the wastage of its resources. This study reviewed recent research progress on the mechanism of R. molle in preventing and treating RA, focusing on its chemical components, anti-inflammatory and analgesic properties and summarized the adverse reactions associated with R. molle, aiming to offer new ideas for finding natural remedies for RA and methods to reduce toxicity while enhancing the effectiveness of R. molle. The study seeks to clarify the safety and efficacy of R. molle and its extracts, providing a theoretical basis for its application prospects and further promoting the development and utilization of R. molle resources.


Assuntos
Artrite Reumatoide , Diterpenos , Rhododendron , Humanos , Rhododendron/química , Artrite Reumatoide/tratamento farmacológico , Anti-Inflamatórios , Diterpenos/farmacologia , Analgésicos
15.
Brain Sci ; 13(11)2023 Oct 24.
Artigo em Inglês | MEDLINE | ID: mdl-38002462

RESUMO

Depression and sleep disturbances are highly prevalent health problems that have been suggested to be associated with vitamin D deficiency. This study investigated whether sleep disturbances affect the association between vitamin D and depressive symptoms. A total of 425 patients with depression were included in this study. Spearman correlation coefficients were chosen to assess the relation between vitamin D concentrations and depressive symptomatology (according to the PHQ-9 and HAMD-17 scores). The GLM Mediation Model in the Medmod module for data analysis in Jamovi 2.2.5 was used to analyze the mediation models for sleep disturbances. Vitamin D concentrations were significantly correlated with PHQ-9 and HAMD-17 scale scores. In addition, item 3 was suggested to have a mediating effect between vitamin D and depressive symptoms in the mediating model of PHQ-9, and item 4 was suggested to have a mediating effect between vitamin D and depressive symptoms in the mediating model of HAMD-17. Sleep disturbances (especially difficulty falling asleep) are mediators between vitamin D and depressive symptoms, suggesting that increasing vitamin D levels at the right time to regulate sleep disturbances may improve depression symptoms, yet further research is necessary.

16.
Sensors (Basel) ; 23(20)2023 Oct 23.
Artigo em Inglês | MEDLINE | ID: mdl-37896748

RESUMO

In this paper, we propose a robust and integrated visual odometry framework exploiting the optical flow and feature point method that achieves faster pose estimate and considerable accuracy and robustness during the odometry process. Our method utilizes optical flow tracking to accelerate the feature point matching process. In the odometry, two visual odometry methods are used: global feature point method and local feature point method. When there is good optical flow tracking and enough key points optical flow tracking matching is successful, the local feature point method utilizes prior information from the optical flow to estimate relative pose transformation information. In cases where there is poor optical flow tracking and only a small number of key points successfully match, the feature point method with a filtering mechanism is used for posing estimation. By coupling and correlating the two aforementioned methods, this visual odometry greatly accelerates the computation time for relative pose estimation. It reduces the computation time of relative pose estimation to 40% of that of the ORB_SLAM3 front-end odometry, while ensuring that it is not too different from the ORB_SLAM3 front-end odometry in terms of accuracy and robustness. The effectiveness of this method was validated and analyzed using the EUROC dataset within the ORB_SLAM3 open-source framework. The experimental results serve as supporting evidence for the efficacy of the proposed approach.

18.
Front Oncol ; 13: 1169979, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37601679

RESUMO

Background: Overexpression of heat shock proteins (HSPs) has been observed in a wide range of human tumors, and there is an increasing evidence demonstrated that HSPs play a key role in tumor progression. Several studies were conducted to explore the clinicopathological characteristics and prognostic value of HSPs in hepatocellular carcinoma (HCC), but the results remain controversial. To address this gap, we conducted a systematic review and meta-analysis. Methods: The eligible literature was obtained from PubMed, Cochrane library, Web of science, Embase, Chinese National Knowledge Infrastructure and Wan Fang databases. We used the odds ratio (OR) and hazard ratio (HR) as the suitable parameters to assess the clinicopathological features and prognostic value of HSPs in HCC patients. Results: The meta-analysis results showed that HSPs expression was associated with overall survival (OS) of HCC patients (HR = 1.61, 95%CI = 1.22-2.13, P=0.001, I 2 = 62.7%). In addition, the pooled results suggested that HSPs expression was significantly correlated with tumor differentiation (OR = 1.33, 95%CI = 1.08-1.65, P = 0.907), vascular invasion (OR = 1.31, 95%CI = 1.02-1.69, P = 0.921) and lymphatic metastasis (OR=1.98, 95%CI= 1.70-2.31, P = 0.740). Meanwhile, the subgroup analysis showed a significant correlation between the expression of HSP27 (HR=1.69, 95%CI = 1.24-2.31, P = 0.674) and HSP90α (HR=2.03, 95%CI = 1.73-2.40, P = 0.743) with OS of HCC patients. Conclusions: Our meta-analysis confirms that HSPs expression is closely associated with a worse prognosis in HCC patients, and may be directly involved in tumor differentiation and distant metastasis. In addition, the subgroup analysis results demonstrate that the expression of HSP27 and HSP90α can be served as potential prognostic predictors of HCC.

19.
Toxins (Basel) ; 15(8)2023 07 28.
Artigo em Inglês | MEDLINE | ID: mdl-37624236

RESUMO

Bacterial lipopolysaccharide (LPS) in the aquatic environment has been reported to cause diseases in red swamp crayfish (Procambarus clarkii). In addition, deoxynivalenol (DON) is one of the primary mycotoxins found in aquaculture. However, the potential synergistic toxic effects of LPS and DON on crayfish are yet to be fully elucidated. In this study, crayfish were exposed to LPS (1 mg kg-1), DON (3 mg kg-1), and their combination (1 mg kg-1 LPS + 3 mg kg-1 DON, L+D) for a duration of six days. Co-exposure to LPS and DON exhibited the lowest survival rate compared to the control or individual treatments with LPS or DON alone. In the initial stage of the experiment, the combined treatment of LPS and DON showed a more pronounced up-regulation of antioxidant and immune-related enzymes in the sera compared to the other treatment groups, with a fold change ranging from 1.3 to 15. In addition, the (L+D) treatment group showed a down-regulation of immune-related genes, as well as Toll pathway-related genes in the hepatopancreas compared to LPS or DON. Moreover, the (L+D) treatment group demonstrated a 100% incidence of histopathological changes in the hepatopancreas, which were significantly more severe compared to the other three groups. In conclusion, our study provides physiological and histopathological evidence that the co-exposure to LPS and DON exerted synergistic toxic effects on crayfish. The observed effects could potentially hinder the development of the crayfish aquaculture industry in China.


Assuntos
Antioxidantes , Astacoidea , Animais , Lipopolissacarídeos/toxicidade , Imunidade
20.
Zhongguo Zhong Yao Za Zhi ; 48(8): 2103-2115, 2023 Apr.
Artigo em Chinês | MEDLINE | ID: mdl-37282899

RESUMO

As a large family of transcription factors, the MYB family plays a vital role in regulating flower development. We studied the MYB family members in Lonicera macranthoides for the first time and identified three sequences of 1R-MYB, 47 sequences of R2R3-MYB, two sequences of 3R-MYB, and one sequence of 4R-MYB from the transcriptome data. Further, their physicochemical properties, conserved domains, phylogenetic relationship, protein structure, functional information, and expression were analyzed. The results show that the 53 MYB transcription factors had different conserved motifs, physicochemical properties, structures, and functions in wild type and 'Xianglei' cultivar of L. macranthoides, indicating their conservation and diversity in evolution. The transcript level of LmMYB was significantly different between the wild type and 'Xianglei' cultivar as well as between flowers and leaves, and some genes were specifically expressed. Forty-three out of 53 LmMYB sequences were expressed in both flowers and leaves, and 9 of the LmMYB members showed significantly different transcript levels between the wild type and 'Xianglei' cultivar, which were up-regulated in the wild type. The results provide a theoretical basis for further studying the specific functional mechanism of the MYB family.


Assuntos
Lonicera , Fatores de Transcrição , Fatores de Transcrição/genética , Fatores de Transcrição/metabolismo , Lonicera/metabolismo , Filogenia , Proteínas de Plantas/metabolismo , Regulação da Expressão Gênica de Plantas
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