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1.
Curr Med Chem ; 2024 Jul 10.
Artigo em Inglês | MEDLINE | ID: mdl-38988155

RESUMO

BACKGROUND: The complex etiology of Ischemia-Reperfusion Injury (IRI) induced by liver transplantation (LT) and the "one-target-focused" method limit the development of effective therapeutic interventions. We aimed to reveal the specific active ingredients and mechanisms involved in the Chinese herb Scutellaria baicalensis Georgi (SBG) in alleviating IRI in LT. METHODS: The active ingredients and potential macromolecular targets of SBG were screened through related databases. The differentially expressed genes of LT were obtained from GSE151648. The protein-protein interaction network was constructed by the STRING database, and Cytoscape 3.7.1 was used to construct a compound-target-disease network. GO and KEGG enrichment analyses were performed on the DAVID database. Finally, the main active components of SBG and the corresponding mechanisms were verified in a donation after circulatory death (DCD) rat LT model. RESULTS: Thirty-two active ingredients of SBG and their targets were identified, and a total of 38 intersection targets were obtained. GO function and KEGG pathway enrichment analyses demonstrated that the plasma membrane and its components play an important role. Molecular docking showed baicalein, the core component of SBG, had a strong binding ability to all hub targets. Next, in DCD rats, baicalein was proven to improve liver function, alleviate pathological injury and apoptosis, and increase the survival rate. Baicalein also significantly affected the expression of 7 hub genes. Furthermore, baicalein could inhibit ferroptosis by inhibiting phospholipid peroxidation. CONCLUSION: Baicalein, the main component of SBG, could alleviate IRI, affect the expression of hub genes, and inhibit ferroptosis in LT.

2.
Plant Sci ; 346: 112177, 2024 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-38964612

RESUMO

The fruit shape of cucumber is an important agronomic trait, and mining regulatory genes, especially dominant ones, is vital for cucumber breeding. In this study, we identified a short and fat fruit mutant, named sff, from an EMS mutagenized population. Compared to the CCMC (WT), sff (MT) exhibited reduced fruit length and increased dimeter. Segregation analysis revealed that the sff phenotype is controlled by a semi-dominant single gene with dosage effects. Through map-based cloning, the SFF locus was narrowed down to a 52.6 kb interval with two SNPs (G651A and C1072T) in the second and third exons of CsaV3_1G039870, which encodes an IQD family protein, CsSUN. The G651A within the IQ domain of CsSUN was identified as the unique SNP among 114 cucumber accessions, and it was the primary cause of the functional alteration in CsSUN. By generating CsSUN knockout lines in cucumber, we confirmed that CsSUN was responsible for sff mutant phenotype. The CsSUN is localized to the plasma membrane. CsSUN exhibited the highest expression in the fruit with lower expression in sff compared to WT. Histological observations suggest that the sff mutant phenotype is due to increased transverse cell division and inhibited longitudinal cell division. Transcriptome analysis revealed that CsSUN significantly affected the expression of genes related to cell division, expansion, and auxin signal transduction. This study unveils CsSUN's crucial role in shaping cucumber fruit and offers novel insights for cucumber breeding.


Assuntos
Cucumis sativus , Frutas , Mutação , Proteínas de Plantas , Cucumis sativus/genética , Cucumis sativus/metabolismo , Cucumis sativus/crescimento & desenvolvimento , Frutas/genética , Frutas/crescimento & desenvolvimento , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismo , Fenótipo , Polimorfismo de Nucleotídeo Único , Regulação da Expressão Gênica de Plantas
3.
Clinics (Sao Paulo) ; 79: 100442, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38996725

RESUMO

OBJECTIVE: To look into the effects of different anesthesia methods on the labor process and the expression of serum estrogen and progesterone in primiparas with painless labor. METHODS: 60 primiparas receiving painless labor were selected as the research objects, and they were divided into either a Spinal & Continuous epidural anesthesia group (n = 30) or a continuous epidural anesthesia group (n = 30), anesthesia is administered using the corresponding anesthesia method. The authors compared serum estrogen and progesterone, inflammatory index expression, pain degree and neonatal health status in different periods. RESULTS: At T2 and T3, serum P, LH, FSH and E2 levels in the Spinal & Continuous epidural anesthesia group were signally lower than those in the Spinal & Continuous epidural anesthesia group (p < 0.05). Spinal & Continuous epidural anesthesia group harbored faster onset and longer duration of sensory block and motor block than the Continuous epidural anesthesia group (p < 0.05). SAS and SDS scores of the Spinal & Continuous epidural anesthesia group were clearly lower than those of the Continuous epidural anesthesia group (p < 0.05). VAS score and serum TNF-α, IL-6 levels of pregnant women in the Spinal & Continuous epidural anesthesia group were memorably lower than those in the Continuous epidural anesthesia group at T2 and T3 (p < 0.05). The total incidence of postoperative complications in the Spinal & Continuous epidural anesthesia group was distinctively lower than that in the Continuous epidural anesthesia group (p < 0.05). CONCLUSION: Spinal anesthesia combined with continuous epidural anesthesia has a better anesthesia effect in the painless labor of primiparas, which can effectually ameliorate the labor process and the expression of serum estrogen and progesterone.


Assuntos
Anestesia Epidural , Estrogênios , Período Pós-Parto , Progesterona , Humanos , Feminino , Gravidez , Progesterona/sangue , Anestesia Epidural/métodos , Adulto , Estrogênios/sangue , Período Pós-Parto/sangue , Trabalho de Parto/sangue , Raquianestesia/métodos , Anestesia Obstétrica/métodos , Adulto Jovem , Fatores de Tempo , Medição da Dor , Paridade , Interleucina-6/sangue , Fator de Necrose Tumoral alfa/sangue
4.
J Immunother Cancer ; 12(7)2024 Jul 11.
Artigo em Inglês | MEDLINE | ID: mdl-38991728

RESUMO

BACKGROUND: Metabolomics has the characteristics of terminal effects and reflects the physiological state of biological diseases more directly. Several current biomarkers of multiple omics were revealed to be associated with immune-related adverse events (irAEs) occurrence. However, there is a lack of reliable metabolic biomarkers to predict irAEs. This study aims to explore the potential metabolic biomarkers to predict risk of irAEs and to investigate the association of plasma metabolites level with survival in patients with lung cancer receiving PD-1/PD-L1 inhibitor treatment. METHODS: The study collected 170 plasmas of 85 patients with lung cancer who received immune checkpoint inhibitors (ICIs) treatment. 58 plasma samples of 29 patients with irAEs were collected before ICIs treatment and at the onset of irAEs. 112 plasma samples of 56 patients who did not develop irAEs were collected before ICIs treatment and plasma matched by treatment cycles to onset of irAEs patients. Untargeted metabolomics analysis was used to identify the differential metabolites before initiating ICIs treatment and during the process that development of irAEs. Kaplan-Meier curves analysis was used to detect the associations of plasma metabolites level with survival of patients with lung cancer. RESULTS: A total of 24 differential metabolites were identified to predict the occurrence of irAEs. Baseline acylcarnitines and steroids levels are significantly higher in patients with irAEs, and the model of eight acylcarnitine and six steroid metabolites baseline level predicts irAEs occurrence with area under the curve of 0.91. Patients with lower concentration of baseline decenoylcarnitine(AcCa(10:1) 2, decenoylcarnitine(AcCa(10:1) 3 and hexanoylcarnitine(AcCa(6:0) in plasma would have better overall survival (OS). Moreover, 52 differential metabolites were identified related to irAEs during ICIs treatment, dehydroepiandrosterone sulfate, corticoserone, cortisol, thyroxine and sphinganine 1-phaosphate were significantly decreased in irAEs group while oxoglutaric acid and taurocholic acid were significantly increased in irAEs group. CONCLUSIONS: High levels of acylcarnitines and steroid hormone metabolites might be risk factor to development of irAEs, and levels of decenoylcarnitine (AcCa(10:1) 2, decenoylcarnitine (AcCa(10:1) 3 and hexanoylcarnitine (AcCa(6:0) could be used to predict OS for patients with lung cancer received ICIs treatment.


Assuntos
Inibidores de Checkpoint Imunológico , Neoplasias Pulmonares , Metabolômica , Humanos , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/sangue , Masculino , Feminino , Inibidores de Checkpoint Imunológico/uso terapêutico , Inibidores de Checkpoint Imunológico/efeitos adversos , Metabolômica/métodos , Idoso , Pessoa de Meia-Idade , Antígeno B7-H1/sangue , Antígeno B7-H1/antagonistas & inibidores , Idoso de 80 Anos ou mais , Receptor de Morte Celular Programada 1/antagonistas & inibidores
5.
Microbiol Spectr ; : e0354923, 2024 Jun 25.
Artigo em Inglês | MEDLINE | ID: mdl-38916335

RESUMO

In recent years, most studies on the gut microbiome have primarily focused on feces samples, leaving the microbial communities in the intestinal mucosa relatively unexplored. To address this gap, our study employed shotgun metagenomics to analyze the microbial compositions in normal rectal mucosa and matched feces from 20 patients with colonic polyps. Our findings revealed a pronounced distinction of the microbial communities between these two sample sets. Compared with feces, the mucosal microbiome contains fewer genera, with Burkholderia being the most discriminating genus between feces and mucosa, highlighting its significant influence on the mucosa. Furthermore, based on the microbial classification and KEGG Orthology (KO) annotation results, we explored the association between rectal mucosal microbiota and factors such as age, gender, BMI, and polyp risk level. Notably, we identified novel biomarkers for these phenotypes, such as Clostridium ramosum and Enterobacter cloacae in age. The mucosal microbiota showed an enrichment of KO pathways related to sugar transport and short chain fatty acid metabolism. Our comprehensive approach not only bridges the knowledge gap regarding the microbial community in the rectal mucosa but also underscores the complexity and specificity of microbial interactions within the human gut, particularly in the Chinese population. IMPORTANCE: This study presents a system-level map of the differences between feces and rectal mucosal microbial communities in samples with colorectal cancer risk. It reveals the unique microecological characteristics of rectal mucosa and its potential influence on health. Additionally, it provides novel insights into the role of the gut microbiome in the pathogenesis of colorectal cancer and paves the way for the development of new prevention and treatment strategies.

6.
Microbiol Res ; 285: 127782, 2024 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-38833832

RESUMO

As a major human and animal pathogen, Staphylococcus aureus can attach to medical implants (abiotic surface) or host tissues (biotic surface), and further establish robust biofilms which enhances resistance and persistence to host immune system and antibiotics. Cell-wall-anchored proteins (CWAPs) covalently link to peptidoglycan, and largely facilitate the colonization of S. aureus on various surfaces (including adhesion and biofilm formation) and invasion into host cells (including adhesion, immune evasion, iron acquisition and biofilm formation). During biofilm formation, CWAPs function in adhesion, aggregation, collagen-like fiber network formation, and consortia formation. In this review, we firstly focus on the structural features of CWAPs, including their intracellular function and interactions with host cells, as well as the functions and ligand binding of CWAPs in different stages of S. aureus biofilm formation. Then, the roles of CWAPs in different biofilm processes with regards in development of therapeutic approaches are clarified, followed by the association between CWAPs genes and clonal lineages. By touching upon these aspects, we hope to provide comprehensive knowledge and clearer understanding on the CWAPs of S. aureus and their roles in biofilm formation, which may further aid in prevention and treatment infection and vaccine development.


Assuntos
Aderência Bacteriana , Proteínas de Bactérias , Biofilmes , Parede Celular , Infecções Estafilocócicas , Staphylococcus aureus , Biofilmes/crescimento & desenvolvimento , Staphylococcus aureus/fisiologia , Staphylococcus aureus/genética , Humanos , Infecções Estafilocócicas/microbiologia , Proteínas de Bactérias/metabolismo , Proteínas de Bactérias/genética , Parede Celular/metabolismo , Animais , Peptidoglicano/metabolismo
7.
J Stroke Cerebrovasc Dis ; 33(8): 107805, 2024 Jun 03.
Artigo em Inglês | MEDLINE | ID: mdl-38839025

RESUMO

BACKGROUND AND OBJECTIVE: Our study aimed to evaluate the associations between platelet count (PC) and in-hospital outcomes for patients with stroke after rt-PA intravenous thrombolysis. METHODS: We identified patients who had been hospitalized with a primary diagnosis of stroke and had received rt-PA intravenous thrombolysis from June 2015 to July 2019 at participating hospitals in the Chinese Stroke Center Alliance. PC measured before intravenous thrombolysis was categorized into the following four groups: severe thrombocytopenia (PC < 100 × 109/L), mild thrombocytopenia (100 ≤ PC < 150 × 109/L), normal PC (150 ≤ PC ≤ 450 × 109/L), and thrombocythemia (PC > 450 × 109/L). Outcomes were determined from clinical data collected during hospitalization. The primary clinical outcome was symptomatic intracranial hemorrhage (sICH). Secondary outcomes were mortality, bleeding events, gastrointestinal (GI) hemorrhage, and in-hospital stroke recurrence. We used multivariate logistic regression models to evaluate the associations between PC and outcomes. RESULTS: We included 44,882 individuals with a median age of 66 years, of whom 34.7 % were female, 951 (2.1 %) had severe thrombocytopenia, 7218 (16.1 %) had mild thrombocytopenia, 36,522 (81.4 %) had a normal PC, and 191 (0.4 %) had thrombocythemia. Both severe and mild thrombocytopenia groups had higher risks of bleeding events (adjusted OR 1.30; 95 % CI,1.01-1.67; p = 0.045; adjusted OR 1.32; 95 % CI,1.19-1.46; p < 0.001) and sICH (adjusted OR 1.48;95 % CI,1.13-1.94; p = 0.005; adjusted OR 1.43;95 % CI,1.27-1.60; p < 0.001) than the normal PC group. Patients with 100 ≤ PC < 150 × 109/L also had a higher risk of in-hospital stroke recurrence (adjusted OR 1.12; 95 % CI,1.02-1.22; p = 0.02). CONCLUSIONS: Intravenous thrombolysis brings a high risk of sICH given PC < 150 × 109/L, especially PC < 100 × 109/L. It indicated that PC < 100 × 109/L is a reasonable contraindication to thrombolysis.

8.
Front Pharmacol ; 15: 1355507, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38720778

RESUMO

Introduction: Solute carrier (SLC) transport proteins play a crucial role in maintaining cellular nutrient and metabolite homeostasis and are implicated in various human diseases, making them potential targets for therapeutic interventions. However, the study of SLCs has been limited due to the lack of suitable tools, particularly cell-based substrate uptake assays, necessary for understanding their biological functions and for drug discovery purposes. Methods: In this study, a cell-based uptake assay was developed using a stable isotope-labeled compound as the substrate for SLCs, with detection facilitated by liquid chromatography-tandem mass spectrometry (LC-MS/MS). This assay aimed to address the limitations of existing assays, such as reliance on hazardous radiolabeled substrates and limited availability of fluorescent biosensors. Results: The developed assay was successfully applied to detect substrate uptakes by two specific SLCs: L-type amino acid transporter 1 (LAT1) and sodium taurocholate co-transporting polypeptide (NTCP). Importantly, the assay demonstrated comparable results to the radioactive method, indicating its reliability and accuracy. Furthermore, the assay was utilized to screen for novel inhibitors of NTCP, leading to the identification of a potential NTCP inhibitor compound. Discussion: The findings highlight the utility of the developed cell-based uptake assay as a rapid, simple, and environmentally friendly tool for investigating SLCs' biological roles and for drug discovery purposes. This assay offers a safer alternative to traditional methods and has the potential to contribute significantly to advancing our understanding of SLC function and identifying therapeutic agents targeting SLC-mediated pathways.

9.
Microbiol Spectr ; 12(6): e0035324, 2024 Jun 04.
Artigo em Inglês | MEDLINE | ID: mdl-38717160

RESUMO

Candida albicans (C. albicans) and Lactiplantibacillus plantarum subsp. plantarum (L. plantarum) are frequently identified in various niches, but their dual-species interaction, especially with C. albicans in yeast form, remains unclear. This study aimed to investigate the dual-species interaction of L. plantarum and C. albicans, including proliferation, morphology, and transcriptomes examined by selective agar plate counting, microscopy, and polymicrobial RNA-seq, respectively. Maintaining a stable and unchanged growth rate, L. plantarum inhibited C. albicans yeast cell proliferation but not hyphal growth. Combining optical microscopy and atomic force microscopy, cell-to-cell direct contact and co-aggregation with L. plantarum cells surrounding C. albicans yeast cells were observed during dual-species interaction. Reduced C. albicans yeast cell proliferation in mixed culture was partially due to L. plantarum cell-free culture supernatant but not the acidic environment. Upon polymicrobial transcriptomics analysis, interesting changes were identified in both L. plantarum and C. albicans gene expression. First, two L. plantarum quorum-sensing systems showed contrary changes, with the activation of lamBDCA and repression of luxS. Second, the upregulation of stress response-related genes and downregulation of cell cycle, cell survival, and cell integrity-related pathways were identified in C. albicans, possibly connected to the stress posed by L. plantarum and the reduced yeast cell proliferation. Third, a large scale of pathogenesis and virulence factors were downregulated in C. albicans, indicating the potential interruption of pathogenic activities by L. plantarum. Fourth, partial metabolism and transport pathways were changed in L. plantarum and C. albicans. The information in this study might aid in understanding the behavior of L. plantarum and C. albicans in dual-species interaction.IMPORTANCEThe anti-Candida albicans activity of Lactiplantibacillus plantarum has been explored in the past decades. However, the importance of C. albicans yeast form and the effect of C. albicans on L. plantarum had also been omitted. In this study, the dual-species interaction of L. plantarum and C. albicans was investigated with a focus on the transcriptomes. Cell-to-cell direct contact and co-aggregation with L. plantarum cells surrounding C. albicans yeast cells were observed. Upon polymicrobial transcriptomics analysis, interesting changes were identified, including contrary changes in two L. plantarum quorum-sensing systems and reduced cell survival-related pathways and pathogenesis determinants in C. albicans.


Assuntos
Candida albicans , Interações Microbianas , Percepção de Quorum , Candida albicans/genética , Candida albicans/patogenicidade , Candida albicans/fisiologia , Candida albicans/metabolismo , Candida albicans/crescimento & desenvolvimento , Percepção de Quorum/genética , Virulência/genética , Lactobacillus plantarum/genética , Lactobacillus plantarum/metabolismo , Lactobacillus plantarum/fisiologia , Regulação Fúngica da Expressão Gênica , Transcriptoma , Fatores de Virulência/genética , Fatores de Virulência/metabolismo
10.
Cell Immunol ; 401-402: 104838, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38810591

RESUMO

BACKGROUND: The NOD-like receptor protein 3 (NLRP3) mediated pyroptosis of macrophages is closely associated with liver ischemia reperfusion injury (IRI). As a covalent inhibitor of NLRP3, Oridonin (Ori), has strong anti-inflammasome effect, but its effect and mechanisms for liver IRI are still unknown. METHODS: Mice and liver macrophages were treated with Ori, respectively. Co-IP and LC-MS/MS analysis of the interaction between PKM2 and NLRP3 in macrophages. Liver damage was detected using H&E staining. Pyroptosis was detected by WB, TEM, and ELISA. RESULTS: Ori ameliorated liver macrophage pyroptosis and liver IRI. Mechanistically, Ori inhibited the interaction between pyruvate kinase M2 isoform (PKM2) and NLRP3 in hypoxia/reoxygenation(H/R)-induced macrophages, while the inhibition of PKM2/NLRP3 reduced liver macrophage pyroptosis and liver IRI. CONCLUSION: Ori exerted protective effects on liver IRI via suppressing PKM2/NLRP3-mediated liver macrophage pyroptosis, which might become a potential therapeutic target in the clinic.


Assuntos
Diterpenos do Tipo Caurano , Fígado , Macrófagos , Camundongos Endogâmicos C57BL , Proteína 3 que Contém Domínio de Pirina da Família NLR , Piroptose , Traumatismo por Reperfusão , Animais , Proteína 3 que Contém Domínio de Pirina da Família NLR/metabolismo , Piroptose/efeitos dos fármacos , Traumatismo por Reperfusão/metabolismo , Traumatismo por Reperfusão/tratamento farmacológico , Camundongos , Fígado/metabolismo , Fígado/efeitos dos fármacos , Fígado/patologia , Macrófagos/metabolismo , Macrófagos/efeitos dos fármacos , Diterpenos do Tipo Caurano/farmacologia , Masculino , Piruvato Quinase/metabolismo , Inflamassomos/metabolismo , Inflamassomos/efeitos dos fármacos , Hepatopatias/metabolismo , Hepatopatias/tratamento farmacológico
11.
J Colloid Interface Sci ; 671: 423-433, 2024 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-38815377

RESUMO

The development of a portable smartphone-based electrochemical sensor for analyzing adrenaline levels in real samples can make a great contribution to the research community worldwide. In order to achieve this goal, the key challenge is to build sensing interfaces with excellent electrocatalytic properties. In this work, microspherical bimetallic metal-organic frameworks (CoNi-MOF) consisting of nanoclusters were first synthesized using a hydrothermal method. On this basis, the catalytic activity of pure chitosan-polyacrylamide hydrogel (CS-PAM) was modulated by adding different amounts of CoNi-MOF during the in-situ synthesis of CS-PAM. Finally, a portable electrochemical detection system based on CS-PAM was established for the detection of adrenaline. A series of resulting composite hydrogels with a large specific surface area, abundant active sites, and unique network structure facilitate the enrichment and catalysis of adrenaline molecules. Under optimal conditions, the analytical platform constructed by using CoNi-MOF-based CS-PAM has the advantages of a wide detection range (0.5-10 and 10-2500 µM), a low detection limit (0.167 µM), and high sensitivity (0.182 and 0.133 µA·µM·cm-2). In addition, the sensor maintains selective detection of the target in the presence of many different types of interferences, and the current response is not significantly reduced even after 60 cycles of testing. We strongly believe that the designed smart portable sensing can realize the accurate determination of adrenaline in complex systems, and this study can provide new ideas for the research of MOFs-based hydrogels in electrochemical analysis.

12.
Neuropharmacology ; 255: 110006, 2024 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-38763325

RESUMO

Currently, there are no effective therapeutic agents available to treat Alzheimer's disease (AD). However, edaravone dexborneol (EDB), a novel composite agent used to treat acute ischemic stroke, has recently been shown to exert efficacious neuroprotective effects. However, whether EDB can ameliorate cognitive deficits in AD currently remains unclear. To this end, we explored the effects of EDB on AD and its potential mechanisms using an AD animal model (male APP/PS1 mice) treated with EDB for 10 weeks starting at 6 months of age. Subsequent analyses revealed that EDB-treated APP/PS1 mice exhibited improved cognitive abilities compared to untreated APP/PS1 mice. Administration of EDB in APP/PS1 mice further alleviated neuropathological alterations of the hippocampus, including Aß deposition, pyramidal cell karyopyknosis, and oxidative damage, and significantly decreased the levels of inflammatory cytokines (IL-1ß, IL-6 and TNF-α) and COX-2 in the hippocampus of APP/PS1 mice. Transcriptome sequencing analysis demonstrated the critical role of the inflammatory reaction in EDB treatment in APP/PS1 mice, indicating that the alleviation of the inflammatory reaction by EDB in the hippocampus of APP/PS1 mice was linked to the action of the TREM2/TLR4/MAPK signaling pathway. Further in vitro investigations showed that EDB suppressed neuroinflammation in LPS-stimulated BV2 cells by inhibiting the TLR4/MAPK signaling pathway and upregulating TREM2 expression. Thus, the findings of the present study demonstrate that EDB is a promising therapeutic agent for AD-related cognitive dysfunction.


Assuntos
Disfunção Cognitiva , Edaravone , Glicoproteínas de Membrana , Receptores Imunológicos , Receptor 4 Toll-Like , Regulação para Cima , Animais , Receptor 4 Toll-Like/metabolismo , Camundongos , Masculino , Disfunção Cognitiva/tratamento farmacológico , Disfunção Cognitiva/metabolismo , Receptores Imunológicos/metabolismo , Receptores Imunológicos/genética , Glicoproteínas de Membrana/metabolismo , Edaravone/farmacologia , Edaravone/uso terapêutico , Regulação para Cima/efeitos dos fármacos , Camundongos Transgênicos , Fármacos Neuroprotetores/farmacologia , Sistema de Sinalização das MAP Quinases/efeitos dos fármacos , Hipocampo/efeitos dos fármacos , Hipocampo/metabolismo , Hipocampo/patologia , Precursor de Proteína beta-Amiloide/genética , Precursor de Proteína beta-Amiloide/metabolismo , Camundongos Endogâmicos C57BL , Doença de Alzheimer/tratamento farmacológico , Doença de Alzheimer/metabolismo , Modelos Animais de Doenças , Presenilina-1/genética
13.
Heliyon ; 10(9): e30169, 2024 May 15.
Artigo em Inglês | MEDLINE | ID: mdl-38699022

RESUMO

Nauclea officinalis, as a Chinese medicine in Hainan province, had the effect of treating lower limb ulcers, burn infections. In this paper, we studied the effect of Strictosamide (STR), the main bioactive compound in Nauclea officinals, on wound healing and explored its internal mechanism. Firstly, the wound healing potential of STR was evaluated in a rat model, demonstrating its ability to expedite wound healing, mitigate inflammatory infiltration, and enhance collagen deposition. Additionally, immunofluorescence analysis revealed that STR up-regulated the expression of CD31 and PCNA. Subsequently, target prediction, protein-protein interaction (PPI), gene ontology (GO), and pathway enrichment analyses were used to obtain potential targets, specific biological processes, and molecular mechanisms of STR for the potential treatment of wound healing. Furthermore, molecular docking was conducted to predict the binding affinity between STR and its associated targets. Additionally, in vivo and in vitro experiments confirmed that STR could increase the expression of P-PI3K, P-AKT and P-mTOR by activating the PI3K/AKT signaling pathway. In summary, this study provided a new explanation for the mechanism by which STR promotes wound healing through network pharmacology, suggesting that STR may be a new candidate for treating wound.

14.
Materials (Basel) ; 17(9)2024 Apr 29.
Artigo em Inglês | MEDLINE | ID: mdl-38730894

RESUMO

In the realm of high-tech materials and energy applications, accurately measuring the transient heat flow at media boundaries and the internal thermal conductivity of materials in harsh heat exchange environments poses a significant challenge when using conventional direct measurement methods. Consequently, the study of photothermal parameter reconstruction in translucent media, which relies on indirect measurement techniques, has crucial practical value. Current research on reconstructing photothermal properties within participating media typically focuses on single-objective or time-invariant properties. There is a pressing need to develop effective methods for the simultaneous reconstruction of time-varying thermal flow fields and internal thermal conductivity at the boundaries of participating media. This paper introduces a computational model based on the numerical simulation theory of internal heat transfer systems in participating media, stochastic particle swarm optimization algorithms, and Kalman filter technology. The model aims to enable the simultaneous reconstruction of various thermal parameters within the target medium. Our results demonstrate that under varying levels of measurement noise, the inversion results for different target parameters exhibit slight oscillations around the true values, leading to a reduction in reconstruction accuracy. However, overall, the model demonstrates robustness and accuracy in ideal conditions, validating its effectiveness.

15.
J Neurol ; 271(7): 4191-4202, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38587636

RESUMO

OBJECTIVE: To investigate the prevalence and intensity of grasp reflexes and to examine changes in these reflexes after shunt surgery in patients with idiopathic normal pressure hydrocephalus (iNPH). METHODS: We enrolled 147 patients with probable iNPH. A standard procedure was used to determine the presence of grasp reflexes, and the intensity of these reflexes was assessed using a four-category classification. Clinical rating scales and their correlation with grasp reflexes were also evaluated. Grasp reflexes were reassessed in 72 patients 1 year after surgery. RESULTS: We found that approximately 50.3% of patients with iNPH exhibited a positive grasp reflex. Among these patients, 69% exhibited bilateral positivity, while the remaining patients showed unilateral positivity. Furthermore, the intensity of the grasp reflex was significantly correlated with the severity of gait and with cognitive, urinary, motor, and behavioural symptoms. Surgical interventions led to a reduction (41.7%) or maintenance (30.6%) of the reflex intensity in 72.3% of iNPH patients. The changes in reflex intensity showed significant positive correlations with changes in the number of steps of the Timed Up and Go test and Trail Making Test-A scores but not with changes in total scores on the iNPH Grading Scale. CONCLUSION: This retrospective study identified grasp reflexes as a highly prevalent phenomenon in patients with iNPH. These reflexes can assist in evaluating the severity of various symptoms, including cognitive, gait, urinary, motor and emotional symptoms.


Assuntos
Hidrocefalia de Pressão Normal , Reflexo , Humanos , Hidrocefalia de Pressão Normal/fisiopatologia , Hidrocefalia de Pressão Normal/cirurgia , Masculino , Feminino , Idoso , Estudos Retrospectivos , Idoso de 80 Anos ou mais , Reflexo/fisiologia , Força da Mão/fisiologia , Índice de Gravidade de Doença , Pessoa de Meia-Idade
16.
Acta Pharmacol Sin ; 2024 Apr 17.
Artigo em Inglês | MEDLINE | ID: mdl-38632318

RESUMO

Frizzled receptors (FZDs) are key contributors intrinsic to the Wnt signaling pathway, activation of FZDs triggering the Wnt signaling cascade is frequently observed in human tumors and intimately associated with an aggressive carcinoma phenotype. It has been shown that the abnormal expression of FZD receptors contributes to the manifestation of malignant characteristics in human tumors such as enhanced cell proliferation, metastasis, chemotherapy resistance as well as the acquisition of cancer stemness. Given the essential roles of FZD receptors in the Wnt signaling in human tumors, this review aims to consolidate the prevailing knowledge on the specific status of FZD receptors (FZD1-10) and elucidate their respective functions in tumor progression. Furthermore, we delineate the structural basis for binding of FZD and its co-receptors to Wnt, and provide a better theoretical foundation for subsequent studies on related mechanisms. Finally, we describe the existing biological classes of small molecule-based FZD inhibitors in detail in the hope that they can provide useful assistance for design and development of novel drug candidates targeted FZDs.

17.
Toxics ; 12(4)2024 Apr 22.
Artigo em Inglês | MEDLINE | ID: mdl-38668527

RESUMO

The sweet potato weevil Cylas formicarius is a notorious underground pest in sweet potato (Ipomoea batatas L.). However, little is known about the effects of cadmium (Cd) stress on weevil biology and resistance to pesticides and biotic agents. Therefore, we fed sweet potato weevils with Cd-contaminated sweet potato and assessed adult food intake and survival and larval developmental duration and mortality rates, as well as resistance to the insecticide spinetoram and susceptibility to the entomopathogenic fungus Beauveria bassiana. With increasing Cd concentration, the number of adult weevil feeding holes, adult survival and life span, and larval developmental duration decreased significantly, whereas larval mortality rates increased significantly. However, at the lowest Cd concentration (30 mg/L), adult feeding was stimulated. Resistance of adult sweet potato weevils to spinetoram increased at low Cd concentration, whereas Cd contamination did not affect sensitivity to B. bassiana. Thus, Cd contamination affected sweet potato weevil biology and resistance, and further studies will investigate weevil Cd accumulation and detoxification mechanisms.

18.
Opt Lett ; 49(8): 1957-1960, 2024 Apr 15.
Artigo em Inglês | MEDLINE | ID: mdl-38621050

RESUMO

In the past two decades, photothermal microscopy (PTM) has achieved sensitivity at the level of a single particle or molecule and has found applications in the fields of material science and biology. PTM is a far-field imaging method; its resolution is restricted by the diffraction limits. In our previous work, the modulated difference PTM (MDPTM) was proposed to improve the lateral resolution, but its resolution improvement was seriously constrained by information loss and artifacts. In this Letter, a deep learning approach of the cycle generative adversarial network (Cycle GAN) is employed for further improving the resolution of PTM, called DMDPTM. The point spread functions (PSFs) of both PTM and MDPTM are optimized and act as the second generator of Cycle GAN. Besides, the relationship between the sample's volume and the photothermal signal is utilized during dataset construction. The images of both PTM and MDPTM are utilized as the inputs of the Cycle GAN to incorporate more information. In the simulation, DMDPTM quantitatively distinguishes a distance of 60 nm between two nanoparticles (each with a diameter of 60 nm), demonstrating a 4.4-fold resolution enhancement over the conventional PTM. Experimentally, the super-resolution capability of DMDPTM is verified by restored images of Au nanoparticles, achieving the resolution of 114 nm. Finally, the DMDPTM is successfully employed for the imaging of carbon nanotubes. Therefore, the DMDPTM will serve as a powerful tool to improve the lateral resolution of PTM.

19.
Anal Methods ; 16(15): 2330-2339, 2024 Apr 18.
Artigo em Inglês | MEDLINE | ID: mdl-38562090

RESUMO

Fatty acids (FAs) are essential molecules in all organisms and are involved in various physiological and pathophysiological processes. Pentafluorobenzyl bromide (PFBBr) is commonly used for FA derivatization for gas chromatography-mass spectrometry (GC-MS) quantification by chemical ionization (CI). While CI is the conventional ionization mode for PFBBr derivatization, the electron ionization (EI) source has also demonstrated efficacy in achieving satisfactory analytical performance for the analysis of PFB esters. In this study, we present a novel approach utilizing PFBBr-derivatization on a GC-EI-MS platform to quantitatively analyze a comprehensive range of 44 fatty acids (FAs) spanning from C2 to C24. The method's sensitivity, precision, accuracy, linearity, recovery, and matrix effect were rigorously validated against predetermined acceptance criteria. In comparison to the conventional CI ionization mode, the utilization of PFBBr-derivatization in GC-EI-MS exhibits a wider range of applications and achieves comparable sensitivity levels to the conventional CI platform. By using this method, we successfully quantified 44 FAs in plasma and feces samples from the mice with deoxynivalenol (DON)-induced kidney injury. Among these, the levels of most FA species were increased in the DON-exposure group compared with the control group. The orthogonal partial least squares discriminant analysis (OPLS-DA) of all the tested FAs showed a visual separation of the two groups, indicating DON exposure resulted in a disturbance of the FA profile in mice. These results indicate that the established method by integration of GC-MS with PFBBr derivatization is an efficient approach to quantify the comprehensive FA profile, which includes short-, medium- and long-chain FAs. In addition, our study provides new insights into the mechanism underlying DON exposure-induced kidney injury.


Assuntos
Elétrons , Ácidos Graxos , Fluorbenzenos , Fluorocarbonos , Animais , Camundongos , Cromatografia Gasosa-Espectrometria de Massas/métodos , Ácidos Graxos/análise , Fezes/química
20.
Biomolecules ; 14(4)2024 Mar 25.
Artigo em Inglês | MEDLINE | ID: mdl-38672409

RESUMO

The remarkable efficacy of cancer immunotherapy has been established in several tumor types. Of the various immunotherapies, PD-1/PD-L1 inhibitors are most extensively used in the treatment of many cancers in clinics. These inhibitors restore the suppressed antitumor immune response and inhibit tumor progression by blocking the PD-1/PD-L1 signaling. However, the low response rate is a major limitation in the clinical application of PD-1/PD-L1 inhibitors. Therefore, combination strategies that enhance the response rate are the need of the hour. In this investigation, PT-100 (also referred to as Talabostat, Val-boroPro, and BXCL701), an orally administered and nonselective dipeptidyl peptidase inhibitor, not only augmented the effectiveness of anti-PD-1 therapy but also significantly improved T immune cell infiltration and reversed the immunosuppressive tumor microenvironment. The combination of PT-100 and anti-PD-1 antibody increased the number of CD4+ and CD8+ T cells. Moreover, the mRNA expression of T cell-associated molecules was elevated in the tumor microenvironment. The results further suggested that PT-100 dramatically reduced the ratio of tumor-associated macrophages. These findings provide a promising combination strategy for immunotherapy in lung cancer.


Assuntos
Carcinoma Pulmonar de Lewis , Receptor de Morte Celular Programada 1 , Microambiente Tumoral , Animais , Camundongos , Carcinoma Pulmonar de Lewis/tratamento farmacológico , Carcinoma Pulmonar de Lewis/imunologia , Carcinoma Pulmonar de Lewis/patologia , Carcinoma Pulmonar de Lewis/metabolismo , Linfócitos T CD8-Positivos/imunologia , Linfócitos T CD8-Positivos/efeitos dos fármacos , Linhagem Celular Tumoral , Dipeptidil Peptidase 4/metabolismo , Inibidores da Dipeptidil Peptidase IV/farmacologia , Inibidores da Dipeptidil Peptidase IV/uso terapêutico , Inibidores de Checkpoint Imunológico/farmacologia , Inibidores de Checkpoint Imunológico/uso terapêutico , Imunoterapia/métodos , Camundongos Endogâmicos C57BL , Receptor de Morte Celular Programada 1/antagonistas & inibidores , Receptor de Morte Celular Programada 1/metabolismo , Microambiente Tumoral/efeitos dos fármacos
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