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1.
Sci Rep ; 14(1): 20451, 2024 09 03.
Artigo em Inglês | MEDLINE | ID: mdl-39227723

RESUMO

Bilirubin is widely recognized to possess antioxidant and anti-inflammatory characteristics. However, the relationship between bilirubin and coronary artery disease (CAD) remains controversial, particularly in individuals receiving Percutaneous Coronary Intervention (PCI). Given that statins may enhance the production of heme oxygenase-1 (HO-1) and bilirubin, we investigated the long-term cardiovascular prognostic role of bilirubin levels elevated by statin use in patients undergoing PCI. Data of 6945 subjects undergoing PCI were enrolled in this study. We divided the patients into two groups based on serum total bilirubin (TB) levels detected prior to PCI. The high TB group consisted of patients with serum TB values > 8.4 µmmol/L, while the low TB group consisted of patients with serum TB values ≤ 8.4 µmmol/L. The median follow-up time was 836 days. Cox proportional hazards models were performed to evaluate the hazard ratios (HRs) and 95% confidence interval (CI) for the incidence of major adverse cardiovascular event (MACE) associated with bilirubin levels. The association between TB levels and risk of MACE was significant [adjusted HR = 0.557, 95% CI (0.59-0.96), p = 0.020). Linear analysis was performed to determine the association between preadmission usage of statin and bilirubin level. The preadmission usage of statin independently linearly increases TB [adjusted-ß = 0.371, 95% CI (0.134-0.608), p = 0.002] and direct bilirubin (DB) [adjusted-ß = 0.411, 95% CI (0.300-0.522), p < 0.001). Mediation analysis demonstrated a direct protective role of preadmission statins treatment (ß = - 0.024, p < 0.01), TB (ß = - 0.003, p < 0.05) and DB (ß = - 0.009, p < 0.05). Furthermore, it was found that TB (4.0%) and DB (12.0%) mediated the relationship between preadmission statins therapy and MACE. Bilirubin has a protective effect against MACE. In patients with normal bilirubin level undergoing elective PCI, preadmission statin use elevated bilirubin levels, which were independently associated with a lower incidence of MACE over the long-term follow-up period.


Assuntos
Bilirrubina , Inibidores de Hidroximetilglutaril-CoA Redutases , Intervenção Coronária Percutânea , Humanos , Bilirrubina/sangue , Masculino , Feminino , Intervenção Coronária Percutânea/efeitos adversos , Inibidores de Hidroximetilglutaril-CoA Redutases/uso terapêutico , Idoso , Prognóstico , Pessoa de Meia-Idade , Doença da Artéria Coronariana/sangue , Fatores de Risco
2.
Neurobiol Dis ; 201: 106659, 2024 Sep 05.
Artigo em Inglês | MEDLINE | ID: mdl-39243826

RESUMO

AIM: Parkinson's disease (PD) tremor is associated with dysfunction in the basal ganglia (BG), cerebellum (CB), and sensorimotor networks (SMN). We investigated tremor-related static functional network connectivity (SFNC) and dynamic functional network connectivity (DFNC) in PD patients. METHODS: We analyzed the resting-state functional MRI data of 21 tremor-dominant Parkinson's disease (TDPD) patients and 29 healthy controls. We compared DFNC and SFNC between the three networks and assessed their associations with tremor severity. RESULTS: TDPD patients exhibited increased SFNC between the SMN and BG networks. In addition, they spent more mean dwell time (MDT) in state 2, characterized by sparse connections, and less MDT in state 4, indicating stronger connections. Furthermore, enhanced DFNC between the CB and SMN was observed in state 2. Notably, the MDT of state 2 was positively associated with tremor scores. CONCLUSION: The enhanced dynamic connectivity between the CB and SMN in TDPD patients suggests a potential compensatory mechanism. However, the tendency to remain in a state of sparse connectivity may contribute to the severity of tremor symptoms.

3.
Sci Rep ; 14(1): 21051, 2024 Sep 09.
Artigo em Inglês | MEDLINE | ID: mdl-39251673

RESUMO

This paper proposes a new impulse excitation technique using a square plate. First, the functional relationship between the modal frequency of the specimen and the geometrical dimensions and mechanical parameters was established by using the finite element method. Then, the continuous functional relationship derived by a homotopy method allowed the frequency ratios to be related to the thickness-to-length ratio and Poisson's ratio. By measuring the frequency ratios and thickness-to-length ratio, Poisson's ratio could be calculated using this functional relationship. When the density and Poisson's ratio were known, Young's modulus could be identified inversely in conjunction with the finite element analysis. Finally, a comparison test between this method and the traditional impulse excitation technique was designed and implemented, and the results showed that this method has advantages in both testing efficiency and accuracy. The study provides a new idea for system identification, which has important application value and promotion significance.

4.
Environ Int ; 192: 109015, 2024 Sep 16.
Artigo em Inglês | MEDLINE | ID: mdl-39312841

RESUMO

BACKGROUND: Cold environments pose serious threats on human health, with increased risk for myocardial infarction, stroke, frostbite, and hypothermia. Acquired cold acclimation is required to minimize cold-induced injures and to improve metabolic health. However, the underlying mechanisms remain to be fully elucidated. OBJECTIVE: We aimed to identify critical amino acids involved in cold acclimation and unmask the regulatory mechanisms. METHODS: A total of twenty male participants were recruited and followed up after 3 months' natural cold exposure. Cold-induced vasodilation (CIVD) tests and clinical biochemical analysis were performed at baseline and after 3-months cold exposure, whilst blood samples were collected, and plasma amino acids were analyzed by targeted metabolomics. To further confirm the effect of lysine on cold tolerance and explain the latent mechanism, mice were challenged with chronic cold exposure for 7 days with lysine supplement, then core and local surface temperature as well as thermogenesis activity were detected. RESULTS: Continuous cold exposure shortened the CIVD onset time and increased the average finger temperature. Levels of the plasma lysine and glycine were decreased in both humans and mice. Venn analysis from three datasets revealed that lysine was the only significantly changed plasma amino acid, which strongly correlated with the altered CIVD. Moreover, mice sustained a relatively higher core temperature and surface temperature in the back, tail and paws upon lysine supplementation. Furthermore, lysine supplementation increased the level of histone H3K18cr and promoted the gene and protein expression of Cpt1a, Cpt2 and Cyp27a1 in liver. CONCLUSION: Our work identified lysine as a critical amino acid for the remodeling of hepatic histone crotonylation that facilitates cold acclimation.

5.
BMC Musculoskelet Disord ; 25(1): 718, 2024 Sep 06.
Artigo em Inglês | MEDLINE | ID: mdl-39242516

RESUMO

OBJECTIVE: To systematically review the clinical efficacy (pain, function, quality of life) and safety of platelet-rich plasma (PRP) in the treatment of frozen shoulder through meta-analysis, and provide evidence-based medical evidence for the effectiveness of PRP in the treatment of frozen shoulder. METHODS: A search was conducted on international databases (Pubmed, Web of science, Embase) and Chinese databases (CNKI, Wanfang, VIP) to search the clinical studies on the efficacy of platelet-rich plasma in treating frozen shoulder (adhesive capsulitis/periarthritis/50 shoulder) and their corresponding references published from inception until January 2024. Thoroughly excluded literature not meeting the predetermined inclusion criteria, extracted relevant data from the literature, and input it into RevMan5.4 for meta-analysis. RESULTS: This study ultimately included 14 RCTs, with a total of 1024 patients. The results showed that PRP has significant advantages compared with control groups in VAS (mean difference (MD) =-0.38, 95% confidence interval(CI)(-0.73, -0.03), P = 0.03), UCLA (MD = 3.31, 95% CI (1.02,5.60),P = 0.005), DASH (MD = -4.94,95% CI (-9.34, -0.53),P = 0.03), SPADI (SPADI Total: MD =-16.87, 95% CI (-22.84, -10.91), P < 0.00001; SPADI Pain: MD =-5.38, 95% CI (-7.80, -2.97), P < 0.0001; SPADI Disability: MD =-11.00, 95% CI (-13.61,-8.39), P < 0.00001), and the active and passive Range of Motion (active flexion: MD = 12.70, 95% CI (7.44, 17.95), P < 0.00001; passive flexion: MD = 9.47, 95% CI(3.80, 15.14), P = 0.001; active extension: MD = 3.45, 95% CI(2.39, 4.50), P < 0.00001; active abduction: MD = 13.54, 95% CI(8.42, 18.67), P < 0.00001; passive abduction: MD = 14.26, 95% CI (5.97, 22.56), P = 0.0008; active internal rotation: MD = 5.16, 95% CI (1.84, 8.48), P = 0.002; passive internal rotation: MD = 3.65, 95% CI(1.15, 6.15), P = 0.004; active external rotation: MD = 10.50, 95% CI(5.47, 15.53), P < 0.0001; passive external rotation: MD = 6.00, 95% CI (1.82, 10.19), P = 0.005) except passive extension (MD = 2.25, 95% CI (-0.77, 5.28), P = 0.14). In terms of safety, most studies reported no adverse effects, and only one study reported common complications of joint puncture such as swelling and pain after treatment in both PRP and control groups. Previous studies have shown a risk of osteonecrosis caused by corticosteroids. Therefore, the safety of PRP treatment is more reliable. CONCLUSION: The results showed that PRP was more durable and safer than corticosteroids and other control groups in the treatment of frozen shoulder. STUDY DESIGN: Systematic review. TRIAL REGISTRATION: PROSPERO CRD42022359444, date of registration: 22-09-2022.


Assuntos
Bursite , Plasma Rico em Plaquetas , Amplitude de Movimento Articular , Humanos , Bursite/complicações , Bursite/fisiopatologia , Bursite/terapia , Medição da Dor , Qualidade de Vida , Ensaios Clínicos Controlados Aleatórios como Assunto , Amplitude de Movimento Articular/fisiologia , Articulação do Ombro/fisiopatologia , Dor de Ombro/diagnóstico , Dor de Ombro/etiologia , Dor de Ombro/fisiopatologia , Dor de Ombro/terapia , Resultado do Tratamento
6.
Biomed Pharmacother ; 180: 117455, 2024 Sep 27.
Artigo em Inglês | MEDLINE | ID: mdl-39341076

RESUMO

INTRODUCTION: This study aims to evaluate the therapeutic effects of sodium octanoate (SO), a medium-chain fatty acid salt, on SIMD in a murine model and to explore its underlying mechanisms. METHODS: Male mice were subjected to sepsis models through two methods: intraperitoneal injection of lipopolysaccharide (LPS) and cecal ligation and punction (CLP). Mice received interval doses of SO every 2 hours or 4 hours for a total of six times or three times after LPS treatment. The relationship between SO and G protein-coupled receptor 84 (GPR84) was evaluated through GEO data analysis and molecular docking studies. DBA/2 mice were used to study the role of the GPR84 protein in the SO-mediated protection. Energy metabolomics was utilized to comprehensively assess the impact of SO on the levels of cardiac energy metabolic products in septic mice. histone modification identification techniques were used to further identify the specific sites of histone modification in the hearts of SO-treated septic mice. RESULTS: SO treatment significantly improved myocardial contractile function, restored the oxidative stress imbalance and enhanced the myocardium's resistance to oxidative injury. SO significantly promotes the expression of GPR84. The loss of GPR84 function markedly attenuates the protective effects of SO. SO enhanced myocardial energy metabolism by promoting the synthesis of acetyl-CoA and upregulating genes involved in fatty acid ß-oxidation which were abolished by medium-chain acyl-CoA dehydrogenase (MCAD) knockdown. SO induced histone acetylation, particularly at H3K123 and H3K80. CONCLUSION: Our study demonstrates that SO exerts protective effects against SIMD through both GPR84-mediated anti-inflammatory and antioxidant actions and GPR84-independent enhancement of myocardial energy metabolism, possibly mediated by MCAD.

7.
Proc Natl Acad Sci U S A ; 121(35): e2405845121, 2024 Aug 27.
Artigo em Inglês | MEDLINE | ID: mdl-39178231

RESUMO

Atherosclerosis is a chronic inflammatory disease of the arterial wall characterized by the accumulation of cholesterol-rich lipoproteins in macrophages. How macrophages commit to proinflammatory polarization under atherosclerosis conditions is not clear. Report here that the level of a circulating protein, leucine-rich alpha-2 glycoprotein 1 (LRG1), is elevated in the atherosclerotic tissue and serum samples from patients with coronary artery disease (CAD). LRG1 stimulated macrophages to proinflammatory M1-like polarization through the activation of extracellular signal-regulated kinase 1/2 (ERK1/2) and c-Jun N-terminal kinase (JNK) pathways. The LRG1 knockout mice showed significantly delayed atherogenesis progression and reduced levels of macrophage-related proinflammatory cytokines in a high-fat diet-induced Apoe-/- mouse atherosclerosis model. An anti-LRG1 neutralizing antibody also effectively blocked LRG1-induced macrophage M1-like polarization in vitro and conferred therapeutic benefits to animals with ApoE deficiency-induced atherosclerosis. LRG1 may therefore serve as an additional biomarker for CAD and targeting LRG1 could offer a potential therapeutic strategy for CAD patients by mitigating the proinflammatory response of macrophages.


Assuntos
Aterosclerose , Glicoproteínas , Macrófagos , Animais , Aterosclerose/patologia , Aterosclerose/genética , Aterosclerose/metabolismo , Aterosclerose/imunologia , Macrófagos/metabolismo , Macrófagos/imunologia , Camundongos , Humanos , Glicoproteínas/metabolismo , Glicoproteínas/genética , Camundongos Knockout , Masculino , Apolipoproteínas E/genética , Apolipoproteínas E/deficiência , Apolipoproteínas E/metabolismo , Modelos Animais de Doenças , Citocinas/metabolismo , Dieta Hiperlipídica/efeitos adversos , Camundongos Endogâmicos C57BL , Doença da Artéria Coronariana/patologia , Doença da Artéria Coronariana/genética , Doença da Artéria Coronariana/metabolismo , Doença da Artéria Coronariana/imunologia , Feminino , Camundongos Knockout para ApoE , Ativação de Macrófagos
8.
PLoS One ; 19(8): e0307218, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-39213439

RESUMO

This paper proposes an optimization scheme for the layout of irregular warehouse spaces based on a class-based storage strategy. Firstly, we transform the irregular warehouse space into several regular rectangular areas. Next, through the class-based storage strategy, we develop an algorithm that converts the non-linear clustering problem of homogeneous shelves into a linear selection problem of different sized regular shelf areas. Finally, a comprehensive shelving clustering algorithm and packing problem with different box sizes selection were constructed, and empirical analysis was conducted based on actual data from Xiangtai Warehouse of State Grid Corporation of China. The results show that the new model not only effectively solves the irregular warehouse layout optimization problem under the class storage strategy but also reduces the complexity of the model and shortens the solution time. It is a universally applicable method with significant value for generalization.


Assuntos
Algoritmos , Análise por Conglomerados , China , Modelos Teóricos
9.
J Phys Chem Lett ; 15(35): 8949-8955, 2024 Sep 05.
Artigo em Inglês | MEDLINE | ID: mdl-39185691

RESUMO

Engineering of the interface between the perovskite and hole transport layer (HTL) has been crucial to achieving high performance. In this study, two interfacial materials, MN-CZ and CN-CZ, are designed by systematically regulating the group substitution site to study the relationship between spatial conformation and the passivation effect. The passivation groups of CN-CZ molecules exhibit a stronger "vector addition" effect, resulting in larger molecular dipoles and enhanced defect passivation and energy level regulation effects. Consequently, the CN-CZ-based perovskite solar cell (PSC) shows a high efficiency of 23.8%, which is much higher than that of the reference device. Meanwhile, the humidity and thermal stability of the unencapsulated device have been significantly improved.

10.
Sci Adv ; 10(32): eadp1890, 2024 Aug 09.
Artigo em Inglês | MEDLINE | ID: mdl-39110806

RESUMO

Surface charges play a fundamental role in physics and chemistry, in particular in shaping the catalytic properties of nanomaterials. However, tracking nanoscale surface charge dynamics remains challenging due to the involved length and time scales. Here, we demonstrate time-resolved access to the nanoscale charge dynamics on dielectric nanoparticles using reaction nanoscopy. We present a four-dimensional visualization of the spatiotemporal evolution of the charge density on individual SiO2 nanoparticles under strong-field irradiation with femtosecond-nanometer resolution. The initially localized surface charges exhibit a biexponential redistribution over time. Our findings reveal the influence of surface charges on surface molecular bonding through quantum dynamical simulations. We performed semi-classical simulations to uncover the roles of diffusion and charge loss in the surface charge redistribution process. Understanding nanoscale surface charge dynamics and its influence on chemical bonding on a single-nanoparticle level unlocks an increased ability to address global needs in renewable energy and advanced health care.

11.
12.
Discov Oncol ; 15(1): 387, 2024 Aug 30.
Artigo em Inglês | MEDLINE | ID: mdl-39212755

RESUMO

BACKGROUND: Lung cancer is a leading public health concern worldwide. Previous evidence suggests that chronic obstructive pulmonary disease (COPD) and asthma may contribute to its development. However, whether these common chronic pulmonary diseases are causal factors of lung cancer remained unclear. METHODS: Summary statistics from genome-wide association studies (GWAS) were used for Mendelian randomization (MR) analysis. Genetic data for COPD were obtained from the Global Biobank Meta-Analysis Initiative, and asthma data were retrieved from the UK Biobank cohort. Suitable instrumental variables were selected based on quality control measures. GWAS summary data for lung cancer were obtained from a large study involved 85,716 participants. MR analysis was performed using various methods, and sensitivity analyses were conducted. Multivariable MR (MVMR) analysis was employed to account for potential confounding factors. RESULTS: Our MR analysis revealed a significant causal association between COPD and lung cancer, including its subtypes such as lung squamous cell carcinoma, lung adenocarcinoma, and small cell lung carcinoma. Genetically predicted COPD was associated with a 64% increased risk of lung cancer and a 2.3 to 2.8-fold increased risk of the different subtypes. However, in the MVMR analysis adjusting for smoking, alcohol drinking, and body mass index, the association between COPD and lung cancer became non-significant. No significant association was observed between asthma (childhood-onset and adult-onset) and lung cancer and its histological subtypes. CONCLUSIONS: Our study suggests a potential causal association between COPD and lung cancer. However, this association became non-significant after adjusting for smoking in the multivariable analysis.

14.
Plant Physiol Biochem ; 215: 108851, 2024 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-39191040

RESUMO

Grape ripe rot is one of the most important diseases caused by Colletotrichum spp. Chinese wild grape (Vitis davidii) is highly resistant to Colletotrichum viniferum infection. But mechanisms underlying the resistance remain largely unclear. In this study, transcriptomic and metabolomic responses of V. davidii to C. viniferum were studied before and after 1, 2, 4, and 6 days of inoculation. C. viniferum infection induced the expression of a large number of defense-related genes. KEGG analysis indicated that the differentially expressed genes (DEGs) were largely those involved in alpha-linolenic acid metabolism, flavonoid biosynthesis, phenylpropanoid biosynthesis, stilbenoid biosynthesis, and other defense-related metabolic pathways. Based on transcriptome data and experimental analysis, we found that jasmonic acid (JA) biosynthesis was closely related to V. davidii resistance to C. viniferum. In addition, many genes related to the synthesis of lignin and phytoalexin resveratrol are upregulated by pathogen infection, and metabolomic analysis showed that there was an increasing accumulation of resveratrol on day 6 of C. viniferum inoculation. Further analysis indicated that transcription factors, such as VdWRKY75 regulated the biosynthesis of lignin and stilbenes. A working model for V. davidii against C. viniferum infection was proposed. The infection of C. viniferum induced JA production, JA along with transcription factors regulated the biosynthesis of secondary metabolites, such as lignin and resveratrol that enhanced plant resistance to C. viniferum. This study elucidated molecular mechanisms underlying the resistance of Chinese wild V. davidii to C. viniferum which can provide a theoretical basis for grape disease resistance breeding.


Assuntos
Colletotrichum , Ciclopentanos , Resistência à Doença , Doenças das Plantas , Transcriptoma , Vitis , Colletotrichum/fisiologia , Ciclopentanos/metabolismo , Resistência à Doença/genética , Perfilação da Expressão Gênica , Regulação da Expressão Gênica de Plantas , Metaboloma , Metabolômica , Oxilipinas/metabolismo , Doenças das Plantas/microbiologia , Doenças das Plantas/genética , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismo , Resveratrol , Vitis/microbiologia , Vitis/genética , Vitis/metabolismo
15.
Adv Healthc Mater ; : e2400466, 2024 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-39091049

RESUMO

Chemical topology provides a unique dimension for making therapeutic protein bioconjugates with native structure and intact function, yet the effects of topology remain elusive. Herein, the design, synthesis, and characterization of therapeutic protein bioconjugates in three topologies (i.e., tadpole, macrocycle, and figure-of-eight), are reported. The interferon α2b (IFN) and albumin binding domain (ABD) are selected as the model proteins for bioconjugation and proof-of-concept. The biosynthesis of these topological isoforms is accomplished via direct expression in cells using SpyTag-SpyCatcher chemistry and/or split-intein-mediated ligation for topology diversification. The corresponding topologies are proven with combined techniques of LC-MS, SDS-PAGE, and controlled proteolytic digestion. While the properties of these topological isoforms are similar in most cases, the figure-of-eight-shaped bioconjugate, f8-IFN-ABD, exhibits the best thermal stability and anti-aggregation properties along with prolonged half-life and enhanced tumor retention relative to the tadpole-shaped control, tadp-IFN-ABD, and the macrocyclic control, c-IFN-ABD, showcasing considerable topological effects. The work expands the topological diversity of proteins and demonstrates the potential advantages of leveraging chemical topology for functional benefits beyond multi-function integration in protein therapeutics.

16.
Small ; : e2405126, 2024 Aug 06.
Artigo em Inglês | MEDLINE | ID: mdl-39106227

RESUMO

Biomass-encapsulated liquid metals (LMs) composite gels have aroused tremendous attention as epidermal smart materials due to their biocompatibility and sustainability. However, they can still not simultaneously possess toughness, adhesion, and recoverability. In this work, the tough, sticky, and recyclable protein-encapsulated LMs organogels (GLMx) are fabricated through the micro-interfacial stabilization of LMs by lignin and the following preparation of food-making inspired gels. With the help of lignin modification, the LMs micro-drops demonstrated uniform dispersion in the protein matrix, as well as dense non-covalent interactions (e.g., H─bond and hydrophobic interaction) with amino acid residues in peptide chains, which endowed the GLMx with high conductivity (≈5.4 S m-1), toughness (≈738.2 kJ m-3), self-adhesiveness (a maximal lap-shear strength of ≈58.3 kPa), and recoverability. By tightly adhering onto human skin, the GLMx can act as epidermal sensors to detect drastic (e.g., joint bending) and subtle body movements (e.g., swallowing) and even recognize handwriting and speaking in real-time. Moreover, the organogels can also harvest solar energy and convert it into heat and electricity, which is promising in self-powered intelligent devices. Thus, this work paves a facile way to prepare protein/LMs composite organogels that are suitable for multiple applications like healthcare, human-robot interactions, and solar energy conversion.

17.
Chem Biol Interact ; 400: 111182, 2024 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-39098740

RESUMO

Depression is a severe mental illness affecting patient's physical and mental health. However, long-term effects of existing therapeutic modalities for depression are not satisfactory. Geniposide is an iridoid compound highly expressed in gardenia jasminoides for removing annoyance. The activity of geniposide against depression has been widely studied while most studies concentrated on the expression levels of gene and protein. Herein, the aim of the present study was to employ non-target metabolomic platform of serum to investigate metabolic changes of depression mice and further verify in hippocampus for analyzing the antidepressant mechanism of geniposide. Then we discovered that 9 metabolites of serum were significantly increased in depressive group (prostaglandin E2, leukotriene C4, arachidonic acid, phosphatidylcholine (PC, 16:0/16:0), LysoPC (18:1 (9Z)/0:0), phosphatidylethanolamine (14:0/16:0), creatine, oleamide and aminomalonic acid) and 6 metabolites were decreased (indoxylsulfuric acid, testosterone, lactic acid, glucose 6-phosphate, leucine and valine). The levels of arachidonic acid, LysoPC, lactic acid and glucose 6-phosphate in hippocampus were consistent change with serum in depression mice. Most of them showed significant tendencies to be normal by geniposide treatment. Metabolic pathway analysis indicated that arachidonic acid metabolism and glucose metabolism were the main pathogenesis for the antidepressant effect of geniposide. In addition, the levels of serum tumor necrosis factor-α and interleukin-1 were increased in depressive mice and reversed after geniposide treatment. This study revealed that abnormal metabolism of inflammatory response and glucose metabolism of the serum and hippocampus involved in the occurrence of depressive disorder and antidepressant effect of geniposide.


Assuntos
Antidepressivos , Depressão , Modelos Animais de Doenças , Glucose , Hipocampo , Inflamação , Iridoides , Animais , Iridoides/farmacologia , Iridoides/uso terapêutico , Depressão/tratamento farmacológico , Depressão/metabolismo , Camundongos , Antidepressivos/farmacologia , Antidepressivos/uso terapêutico , Masculino , Hipocampo/metabolismo , Hipocampo/efeitos dos fármacos , Inflamação/tratamento farmacológico , Inflamação/metabolismo , Glucose/metabolismo , Metabolômica
18.
Heliyon ; 10(12): e33214, 2024 Jun 30.
Artigo em Inglês | MEDLINE | ID: mdl-39021924

RESUMO

Background: The pathogenesis of multiple sclerosis (MS) may be closely related to immune regulation and inflammatory cytokines induced by specific flora. Repairing the intestinal flora may alter the immune response in MS patients, thus opening up novel approaches for the treatment of MS. Objective: We aimed to test the therapeutic effect of fecal microbiota transplantation (FMT) on experimental autoimmune encephalomyelitis (EAE) and the characteristics of intestinal microbiota composition changes, explore the potential mechanisms of FMT treatment. Methods: EAE animals were treated with FMT, with the therapeutic effects were evaluated by observing neurological scores and measuring serum levels of cortisol, IL-17, and TLR-2. Fecal microbiome 16S rRNA sequencing was used to profile changes in microbiota composition, and adrenalectomy pretreatment was used to test whether FMT effects were dependent on HPA axis function. Results: FMT improved neurological function and reduced serum IL-17 to levels that were close to the control group. FMT reestablished intestinal homeostasis by altering the structure of the intestinal flora, increasing the abundance of beneficial flora, and regulating intestinal metabolites. We found that the therapeutic effects of FMT depended partly on the efferent function of the HPA axis; surgical disruption of the HPA axis altered the abundance and diversity of the intestinal flora. Conclusion: FMT showed a neuroprotective effect on EAE by increasing the abundance of the beneficial flora, rebuilding intestinal homeostasis, reducing IL-17 and cortisol serum levels, and promoting serum TLR-2; the therapeutic effect of FMT on EAE is partly dependent on the HPA axis.

19.
Int J Appl Earth Obs Geoinf ; 131: 103949, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38993519

RESUMO

Timely and precise detection of emerging infections is imperative for effective outbreak management and disease control. Human mobility significantly influences the spatial transmission dynamics of infectious diseases. Spatial sampling, integrating the spatial structure of the target, holds promise as an approach for testing allocation in detecting infections, and leveraging information on individuals' movement and contact behavior can enhance targeting precision. This study introduces a spatial sampling framework informed by spatiotemporal analysis of human mobility data, aiming to optimize the allocation of testing resources for detecting emerging infections. Mobility patterns, derived from clustering point-of-interest and travel data, are integrated into four spatial sampling approaches at the community level. We evaluate the proposed mobility-based spatial sampling by analyzing both actual and simulated outbreaks, considering scenarios of transmissibility, intervention timing, and population density in cities. Results indicate that leveraging inter-community movement data and initial case locations, the proposed Case Flow Intensity (CFI) and Case Transmission Intensity (CTI)-informed spatial sampling enhances community-level testing efficiency by reducing the number of individuals screened while maintaining a high accuracy rate in infection identification. Furthermore, the prompt application of CFI and CTI within cities is crucial for effective detection, especially in highly contagious infections within densely populated areas. With the widespread use of human mobility data for infectious disease responses, the proposed theoretical framework extends spatiotemporal data analysis of mobility patterns into spatial sampling, providing a cost-effective solution to optimize testing resource deployment for containing emerging infectious diseases.

20.
BMC Plant Biol ; 24(1): 626, 2024 Jul 03.
Artigo em Inglês | MEDLINE | ID: mdl-38961401

RESUMO

BACKGROUND: The calmodulin (CaM) and calmodulin-like (CML) proteins play regulatory roles in plant growth and development, responses to biotic and abiotic stresses, and other biological processes. As a popular fruit and ornamental crop, it is important to explore the regulatory mechanism of flower and fruit development of passion fruit. RESULTS: In this study, 32 PeCaM/PeCML genes were identified from passion fruit genome and were divided into 9 groups based on phylogenetic analysis. The structural analysis, including conserved motifs, gene structure and homologous modeling, illustrates that the PeCaM/PeCML in the same subgroup have relative conserved structural features. Collinearity analysis suggested that the expansion of the CaM/CML gene family likely took place mainly by segmental duplication, and the whole genome replication events were closely related with the rapid expansion of the gene group. PeCaM/PeCMLs were potentially required for different floral tissues development. Significantly, PeCML26 had extremely high expression levels during ovule and fruit development compared with other PeCML genes, suggesting that PeCML26 had potential functions involved in the development of passion fruit flowers and fruits. The co-presence of various cis-elements associated with growth and development, hormone responsiveness, and stress responsiveness in the promoter regions of these PeCaM/PeCMLs might contribute to their diverse regulatory roles. Furthermore, PeCaM/PeCMLs were also induced by various abiotic stresses. This work provides a comprehensive understanding of the CaM/CML gene family and valuable clues for future studies on the function and evolution of CaM/CML genes in passion fruit. CONCLUSION: A total of 32 PeCaM/PeCML genes were divided into 9 groups. The PeCaM/PeCML genes showed differential expression patterns in floral tissues at different development stages. It is worth noting that PeCML26, which is highly homologous to AtCaM2, not only interacts with multiple BBR-BPC TFs, but also has high expression levels during ovule and fruit development, suggesting that PeCML26 had potential functions involved in the development of passion fruit flowers and fruits. This research lays the foundation for future investigations and validation of the potential function of PeCaM/PeCML genes in the growth and development of passion fruit.


Assuntos
Calmodulina , Flores , Frutas , Passiflora , Filogenia , Proteínas de Plantas , Passiflora/genética , Passiflora/crescimento & desenvolvimento , Flores/genética , Flores/crescimento & desenvolvimento , Flores/metabolismo , Frutas/genética , Frutas/crescimento & desenvolvimento , Frutas/metabolismo , Calmodulina/genética , Calmodulina/metabolismo , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismo , Regulação da Expressão Gênica de Plantas , Genoma de Planta , Genes de Plantas , Perfilação da Expressão Gênica
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