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2.
Biomed Pharmacother ; 175: 116755, 2024 May 20.
Artigo em Inglês | MEDLINE | ID: mdl-38772155

RESUMO

With the increasing prevalence of type 2 diabetes mellitus (T2DM), it has become critical to identify effective treatment strategies. In recent years, the novel oral hypoglycaemic drug Imeglimin has attracted much attention in the field of diabetes treatment. The mechanisms of its therapeutic action are complex and are not yet fully understood by current research. Current evidence suggests that pancreatic ß-cells, liver, and skeletal muscle are the main organs in which Imeglimin lowers blood glucose levels and that it acts mainly by targeting mitochondrial function, thereby inhibiting hepatic gluconeogenesis, enhancing insulin sensitivity, promoting pancreatic ß-cell function, and regulating energy metabolism. There is growing evidence that the drug also has a potentially volatile role in the treatment of diabetic complications, including metabolic cardiomyopathy, diabetic vasculopathy, and diabetic neuroinflammation. According to available clinical studies, its efficacy and safety profile are more evident than other hypoglycaemic agents, and it has synergistic effects when combined with other antidiabetic drugs, and also has potential in the treatment of T2DM-related complications. This review aims to shed light on the latest research progress in the treatment of T2DM with Imeglimin, thereby providing clinicians and researchers with the latest insights into Imeglimin as a viable option for the treatment of T2DM.

3.
J Biol Chem ; : 107395, 2024 May 18.
Artigo em Inglês | MEDLINE | ID: mdl-38768812

RESUMO

B2 haplotype MHC has been extensively reported to confer resistance to various avian diseases. But its peptide-binding motif is unknown and the presenting peptide is rarely identified. Here, we identified the peptide-binding motif of B2 haplotype MHC Ⅰ molecules (X-A/V/I/L/P/S/G-X-X-X-X-X-X-V/I/L) in vitro using Random Peptide Library-based MHC-Ⅰ LC-MS/MS analysis. To further clarify the structure basis of the peptide binding motif, we determined the crystal structure of the BF2*02:01-PB2552-560 complex at 1.9 Šresolution. We found that BF2*02:01 had a relatively wide antigen-binding groove, and the structural characterization of pockets of BF2*02:01 was consistent with the characterization of peptide-binding motif. The wider features of the peptide-binding motif and increased number of peptides bound by BF2*02:01 than BF2*04:01 might resolve the puzzles for the presence of potential H9N2 resistance in B2 chickens. Afterwards, we explored the H9N2 AIV-induced cellular immune response in B2 haplotype chickens in vivo. We found that ratio of CD8+ T cell and kinetic expression of cytotoxicity genes including Granzyme K, IFN-γ, NK lysin, and PARP in PBMCs were significantly increased in defending against H9N2 AIV infection. Especially, we selected 411 epitopes as candidate epitopes based on the peptide-binding motif and further identified four CD8+ T-cell epitopes on H9N2 AIV including NS198-106, PB2552-560, NP182-190, and NP455-463 via ELI-spot IFN-γ detections after stimulating memory lymphocytes with peptides. More importantly, these epitopes were found to be conserved in H7N9 AIV and H9N2 AIV. These findings provide direction for developing effective T cell epitope vaccines using well-conserved internal viral antigens in chickens.

5.
Bioresour Technol ; 402: 130767, 2024 Apr 30.
Artigo em Inglês | MEDLINE | ID: mdl-38692373

RESUMO

The study assessed the effect of salinity and lead (Pb(II)) on the anammox sludge for nitrogen removal from saline wastewater. Results showed decreased nitrogen removal and specific anammox activity (SAA) with elevated salinity and Pb(II). SAA reduced from 541.3 ± 4.3 mg N g-1 VSS d-1 at 0.5 mg/L Pb(II) to 436.0 ± 0.2 mg N g-1 VSS d-1 at 30 g/L NaCl, further to 303.6 ± 7.1 mg N g-1 VSS d-1 under 30 g/L NaCl + 0.5 mg/L Pb(II). Notably, the combined inhibition at salinity (15-20 g/L NaCl) and Pb(II) (0.3-0.4 mg/L) exhibited synergistic effect, while higher salinity and Pb(II) aligned with independent inhibition models. Combined inhibition decreased protein/polysaccharides ratio, indicating more severe negative effect on anammox aggregation capacity. Metagenomics confirmed decreased Candidatus Kuenenia, and enhanced denitrification under elevated salinity and Pb(II) conditions. This study offers insights into anammox operation for treating saline wastewater with heavy metals.

6.
Front Immunol ; 15: 1394925, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38690282

RESUMO

Sepsis is a life-threatening organ dysfunction caused by the host's dysfunctional response to infection. Abnormal activation of the immune system and disturbance of energy metabolism play a key role in the development of sepsis. In recent years, the Sirtuins (SIRTs) family has been found to play an important role in the pathogenesis of sepsis. SIRTs, as a class of histone deacetylases (HDACs), are widely involved in cellular inflammation regulation, energy metabolism and oxidative stress. The effects of SIRTs on immune cells are mainly reflected in the regulation of inflammatory pathways. This regulation helps balance the inflammatory response and may lessen cell damage and organ dysfunction in sepsis. In terms of energy metabolism, SIRTs can play a role in immunophenotypic transformation by regulating cell metabolism, improve mitochondrial function, increase energy production, and maintain cell energy balance. SIRTs also regulate the production of reactive oxygen species (ROS), protecting cells from oxidative stress damage by activating antioxidant defense pathways and maintaining a balance between oxidants and reducing agents. Current studies have shown that several potential drugs, such as Resveratrol and melatonin, can enhance the activity of SIRT. It can help to reduce inflammatory response, improve energy metabolism and reduce oxidative stress, showing potential clinical application prospects for the treatment of sepsis. This review focuses on the regulation of SIRT on inflammatory response, energy metabolism and oxidative stress of immune cells, as well as its important influence on multiple organ dysfunction in sepsis, and discusses and summarizes the effects of related drugs and compounds on reducing multiple organ damage in sepsis through the pathway involving SIRTs. SIRTs may become a new target for the treatment of sepsis and its resulting organ dysfunction, providing new ideas and possibilities for the treatment of this life-threatening disease.


Assuntos
Metabolismo Energético , Estresse Oxidativo , Sepse , Sirtuínas , Humanos , Sepse/tratamento farmacológico , Sepse/imunologia , Sepse/metabolismo , Animais , Sirtuínas/metabolismo , Metabolismo Energético/efeitos dos fármacos , Espécies Reativas de Oxigênio/metabolismo , Inflamação/tratamento farmacológico , Inflamação/imunologia
7.
Water Res ; 256: 121646, 2024 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-38657309

RESUMO

Sewage treatment processes are a critical anthropogenic source of bioaerosols and may present significant health risks to plant workers. Compared with the specialization and scale of urban sewage treatment, many decentralized treatment models are flexible and extensive. These treatment facilities are usually close to residential areas owing to the pipe network layout and other restrictions. Bioaerosols generated by these facilities may present a serious and widespread occupational and non-occupational exposure risk to nearby residents, particularly the elderly and children. An understanding of the characteristics and exposure risks of bioaerosols produced during decentralized sewage treatment is lacking. We compared bioaerosol emission characteristics and potential exposure risks under four decentralized sewage discharge methods and treatment models: small container collection (SCC), open-channel discharge (OCD), single household/combined treatment (SHCT), and centralized treatment (CT) in northwest China. The OCD mode had the highest bioaerosol production, whereas the CT mode had the lowest. The OCD model contained the most pathogenic bacterial species, up to 43 species, including Sphingomonas, Pseudomonas, Cladosporium, and Alternaria. Risk assessments indicated bioaerosol exposure was lower in the models with sewage treatment (SHCT and CT) than in those without (SCC and OCD). Different populations exhibited large variations in potential risks owing to differences in time spent indoors and outdoors. The highest risk was observed in males exposed to the SCC model. This study provides a theoretical basis and theories for the future joint prevention and control of the bioaerosol exposure risk from decentralized sewage treatment.


Assuntos
Aerossóis , Microbiologia do Ar , Esgotos , Esgotos/microbiologia , Eliminação de Resíduos Líquidos , China , Humanos , Medição de Risco , Bactérias
8.
Natl Sci Rev ; 11(4): nwae043, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38650829

RESUMO

For sessile plants, gene expression plays a pivotal role in responding to salinity stress by activating or suppressing specific genes. However, our knowledge of genetic variations governing gene expression in response to salt stress remains limited in natural germplasm. Through transcriptome analysis of the Global Mini-Core Rice Collection consisting of a panel of 202 accessions, we identified 22 345 and 27 610 expression quantitative trait loci associated with the expression of 7787 and 9361 eGenes under normal and salt-stress conditions, respectively, leveraging the super pan-genome map. Notably, combined with genome-wide association studies, we swiftly pinpointed the potential candidate gene STG5-a major salt-tolerant locus known as qSTS5. Intriguingly, STG5 is required for maintaining Na+/K+ homeostasis by directly regulating the transcription of multiple members of the OsHKT gene family. Our study sheds light on how genetic variants influence the dynamic changes in gene expression responding to salinity stress and provides a valuable resource for the mining of salt-tolerant genes in the future.

9.
Zhongguo Zhong Yao Za Zhi ; 49(3): 770-778, 2024 Feb.
Artigo em Chinês | MEDLINE | ID: mdl-38621881

RESUMO

This paper aims to study the therapeutic effect of Massa Medicata Fermentata on hyperlipidemia model rats and investigate its mechanism of hypolipidemic effect with the help of non-targeted metabolomics. The mixed hyperlipidemia model rats were constructed by giving high-fat chow. After successful modeling, the rats were divided into the model group, pravastatin sodium group(4.4 mg·kg~(-1)), lipotropic group(0.1 g·kg~(-1)), high-dose group(2.4 g·kg~(-1)), medium-dose group(1.2 g·kg~(-1)), and low-dose group(0.6 g·kg~(-1)) of Massa Medicata Fermentata, and they were administered for four weeks once daily. An equal volume of ultrapure water was given to the blank group and model group. Serum lipid level and liver hematoxylin-eosin(HE) staining were used as indicators to estimate the intervention effect of Massa Medicata Fermentata on mixed hyperlipidemia, and the changes in metabolites in plasma of mixed hyperlipidemia model rats were analyzed by non-targeted metabolomics. The mechanism of the hypolipidemic effect of Massa Medicata Fermentata was analyzed through metabolite pathway enrichment. The results showed that compared with the model group, the Massa Medicata Fermentata administration group, especially the high-dose group, could significantly reduce the content of total cholesterol(TC), triglyceride(TG), and low-density lipoprotein cholesterol(LDL-c)(P<0.05 or P<0.01), and liver HE staining revealed that the number of adipocytes in the high-dose group was reduced to some extent. The potential biomarkers obtained by non-targeted metabolomics screening included glycerol 3-phosphate, sphingomyelin, sphingosine 1-phosphate, and deoxyuridine, which were mainly involved in the sphingolipid metabolism process, glycerophospholipid metabolism process, glycerol ester metabolism pathway, and pyrimidine metabolism pathway, totaling four possible metabolic pathways related to lipid metabolism. This study provides a reference for an in-depth investigation of the hypolipidemic mechanism of Massa Medicata Fermentata, which is of great significance for further promoting the clinical application of Massa Medicata Fermentata and increasing the indications.


Assuntos
Medicamentos de Ervas Chinesas , Hiperlipidemias , Ratos , Animais , Medicamentos de Ervas Chinesas/farmacologia , Fígado , Hiperlipidemias/tratamento farmacológico , Metabolômica , Colesterol , Dieta Hiperlipídica/efeitos adversos
10.
bioRxiv ; 2024 Mar 20.
Artigo em Inglês | MEDLINE | ID: mdl-38562799

RESUMO

To uncover the intricate, chemotherapy-induced spatiotemporal remodeling of the tumor microenvironment, we conducted integrative spatial and molecular characterization of 97 high-grade serous ovarian cancer (HGSC) samples collected before and after chemotherapy. Using single-cell and spatial analyses, we identify increasingly versatile immune cell states, which form spatiotemporally dynamic microcommunities at the tumor-stroma interface. We demonstrate that chemotherapy triggers spatial redistribution and exhaustion of CD8+ T cells due to prolonged antigen presentation by macrophages, both within interconnected myeloid networks termed "Myelonets" and at the tumor stroma interface. Single-cell and spatial transcriptomics identifies prominent TIGIT-NECTIN2 ligand-receptor interactions induced by chemotherapy. Using a functional patient-derived immuno-oncology platform, we show that CD8+T-cell activity can be boosted by combining immune checkpoint blockade with chemotherapy. Our discovery of chemotherapy-induced myeloid-driven spatial T-cell exhaustion paves the way for novel immunotherapeutic strategies to unleash CD8+ T-cell-mediated anti-tumor immunity in HGSC.

11.
J Mater Chem B ; 12(17): 4097-4117, 2024 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-38587869

RESUMO

Single phototherapy and immunotherapy have individually made great achievements in tumor treatment. However, monotherapy has difficulty in balancing accuracy and efficiency. Combining phototherapy with immunotherapy can realize the growth inhibition of distal metastatic tumors and enable the remote monitoring of tumor treatment. The development of nanomaterials with photo-responsiveness and anti-tumor immunity activation ability is crucial for achieving photo-immunotherapy. As immune adjuvants, photosensitizers and photothermal agents, manganese-based nanoparticles (Mn-based NPs) have become a research hotspot owing to their multiple ways of anti-tumor immunity regulation, photothermal conversion and multimodal imaging. However, systematic studies on the synergistic photo-immunotherapy applications of Mn-based NPs are still limited; especially, the green synthesis and mechanism of Mn-based NPs applied in immunotherapy are rarely comprehensively discussed. In this review, the synthesis strategies and function of Mn-based NPs in immunotherapy are first introduced. Next, the different mechanisms and leading applications of Mn-based NPs in immunotherapy are reviewed. In addition, the advantages of Mn-based NPs in synergistic photo-immunotherapy are highlighted. Finally, the challenges and research focus of Mn-based NPs in combination therapy are discussed, which might provide guidance for future personalized cancer therapy.


Assuntos
Imunoterapia , Manganês , Humanos , Manganês/química , Manganês/farmacologia , Imunoterapia/métodos , Fototerapia/métodos , Química Verde , Neoplasias/terapia , Neoplasias/tratamento farmacológico , Animais , Nanoestruturas/química , Fármacos Fotossensibilizantes/química , Fármacos Fotossensibilizantes/farmacologia , Fármacos Fotossensibilizantes/síntese química , Antineoplásicos/química , Antineoplásicos/farmacologia , Antineoplásicos/síntese química , Tamanho da Partícula
12.
Langmuir ; 40(18): 9761-9774, 2024 May 07.
Artigo em Inglês | MEDLINE | ID: mdl-38663878

RESUMO

Stimuli-responsive behaviors and controlled release in liposomes are pivotal in nanomedicine. To this end, we present an approach using a photoresponsive azobenzene nanocluster (AzDmpNC), prepared from azobenzene compounds through melting and aggregation. When integrated with liposomes, they form photoresponsive vesicles. The morphology and association with liposomes were investigated by using transmission electron microscopy. Liposomes loaded with calcein exhibited a 9.58% increased release after UV exposure. To gain insights into the underlying processes and elucidate the mechanisms involved. The molecular dynamic simulations based on the reactive force field and all-atom force field were employed to analyze the aggregation of isomers into nanoclusters and their impacts on phospholipid membranes, respectively. The results indicate that the nanoclusters primarily aggregate through π-π and T-stacking forces. The force density inside the cis-isomer of AzDmpNC formed after photoisomerization is lower, leading to its easier dispersion, rapid diffusion, and penetration into the membrane, disrupting the densification.


Assuntos
Compostos Azo , Lipossomos , Simulação de Dinâmica Molecular , Compostos Azo/química , Compostos Azo/efeitos da radiação , Lipossomos/química , Nanopartículas/química , Raios Ultravioleta , Fluoresceínas/química , Processos Fotoquímicos
13.
Mol Plant ; 17(5): 772-787, 2024 May 06.
Artigo em Inglês | MEDLINE | ID: mdl-38581129

RESUMO

The phytohormone auxin plays a pivotal role in governing plant growth and development. Although the TRANSPORT INHIBITOR RESPONSE1/AUXIN SIGNALING F-BOX (TIR1/AFB) receptors function in both the nucleus and cytoplasm, the mechanism governing the distribution of TIR1/AFBs between these cellular compartments remains unknown. In this study, we demonstrate that auxin-mediated oxidation of TIR1/AFB2 is essential for their targeting to the nucleus. We showed that small active molecules, reactive oxygen species (ROS) and nitric oxide (NO), are indispensable for the nucleo-cytoplasmic distribution of TIR1/AFB2 in trichoblasts and root hairs. Further studies revealed that this process is regulated by the FERONIA receptor kinase-NADPH oxidase signaling pathway. Interestingly, ROS and NO initiate oxidative modifications in TIR1C140/516 and AFB2C135/511, facilitating their subsequent nuclear import. The oxidized forms of TIR1C140/516 and AFB2C135/511 play a crucial role in enhancing the function of TIR1 and AFB2 in transcriptional auxin responses. Collectively, our study reveals a novel mechanism by which auxin stimulates the transport of TIR1/AFB2 from the cytoplasm to the nucleus, orchestrated by the FERONIA-ROS signaling pathway.


Assuntos
Proteínas de Arabidopsis , Arabidopsis , Proteínas F-Box , Ácidos Indolacéticos , Oxirredução , Receptores de Superfície Celular , Transdução de Sinais , Arabidopsis/metabolismo , Ácidos Indolacéticos/metabolismo , Proteínas F-Box/metabolismo , Receptores de Superfície Celular/metabolismo , Proteínas de Arabidopsis/metabolismo , Espécies Reativas de Oxigênio/metabolismo , Núcleo Celular/metabolismo , Óxido Nítrico/metabolismo , Fosfotransferases/metabolismo , Regulação da Expressão Gênica de Plantas , Proteínas Serina-Treonina Quinases
14.
Front Neurosci ; 18: 1308627, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38595969

RESUMO

Background: The 2021 World Health Organization Classification of Central Nervous System Tumors updates glioma subtyping and grading system, and incorporates EGFR amplification (Amp) as one of diagnostic markers for glioblastoma (GBM). Purpose: This study aimed to describe the frequency, clinical value and molecular correlation of EGFR Amp in diffuse gliomas based on the latest classification. Methods: We reviewed glioma patients between 2011 and 2022 at our hospital, and included 187 adult glioma patients with available tumor tissue for detection of EGFR Amp and other 59 molecular markers of interest. Clinical, radiological and pathological data was analyzed based on the status of EGFR Amp in different glioma subtypes. Results: 163 gliomas were classified as adult-type diffuse gliomas, and the number of astrocytoma, oligodendroglioma and GBM was 41, 46, and 76. EGFR Amp was more common in IDH-wildtype diffuse gliomas (66.0%) and GBM (85.5%) than IDH-mutant diffuse gliomas (32.2%) and its subtypes (astrocytoma, 29.3%; oligodendroglioma, 34.8%). EGFR Amp did not stratify overall survival (OS) in IDH-mutant diffuse gliomas and astrocytoma, while was significantly associated with poorer OS in IDH-wildtype diffuse gliomas, histologic grade 2 and 3 IDH-wildtype diffuse astrocytic gliomas and GBM. Conclusion: Our study validated EGFR Amp as a diagnostic marker for GBM and still a useful predictor for shortened OS in this group.

15.
J Clin Ultrasound ; 2024 Apr 24.
Artigo em Inglês | MEDLINE | ID: mdl-38655706

RESUMO

PURPOSE: To analyze the influence of RV dysfunction evaluated by Free-angle M-mode (FAM) TAPSE Z-score on retrograde ductus arteriosus flow (RDAF) in fetuses with Ebstein anomaly (EA). METHODS: A retrospective cohort study of 30 EA and 60 normal fetuses were enrolled. The EA group was divided into two groups: with RDAF (EA-RDAF group) and without RDAF (EA-NRDAF group). FAM was used to measure TAPSE of EA and normal fetuses, and Z-scores were calculated. The differences of FAM-TAPSE Z-score, gestational week (GW), maternal age (MA), and mitral valve-tricuspid valve distance (MTD) between three groups were compared. The correlation and binary logistic regression between FAM-TAPSE Z-score, GW, MA, MTD, and RDAF were analyzed. RESULTS: FAM-TAPSE Z-score was significantly lower in EA-RDAF group compared to other groups (p < 0.05). FAM-TAPSE Z-score, GW, and MA were negatively correlated with RDAF (p < 0.05), but no correlation was found between TR, MDT, and RDAF (p > 0.05). Multivariate logistic regression showed that FAM-TAPSE Z-score was an independent influencing factor for RDAF (OR = 0.102, p < 0.05). CONCLUSION: RV dysfunction is an independent factor leading to RDAF in EA fetus, which provides a feasible theoretical basis for further study on improvement of RV function through intrauterine treatment to delay and prevent the RDAF, to avoid death cycle and improve live-birth rate.

16.
Sensors (Basel) ; 24(6)2024 Mar 11.
Artigo em Inglês | MEDLINE | ID: mdl-38544055

RESUMO

Aiming at the traditional single sensor vibration signal cannot fully express the bearing running state, and in the high noise background, the traditional algorithm is insufficient for fault feature extraction. This paper proposes a fault diagnosis algorithm based on multi-sensor and hybrid multimodal feature fusion to achieve high-precision fault diagnosis by leveraging the operating state information of bearings in a high-noise environment to the fullest extent possible. First, the horizontal and vertical vibration signals from two sensors are fused using principal component analysis, aiming to provide a more comprehensive description of the bearing's operating condition, followed by data set segmentation. Following fusion, time-frequency feature maps are generated using a continuous wavelet transform for global time-frequency feature extraction. A first diagnostic model is then developed utilizing a residual neural network. Meanwhile, the feature data is normalized, and 28 time-frequency feature indexes are extracted. Subsequently, a second diagnostic model is constructed using a support vector machine. Lastly, the two diagnosis models are integrated to derive the final model through an ensemble learning algorithm fused at the decision level and complemented by a genetic algorithm solution to improve the diagnosis accuracy. Experimental results demonstrate the effectiveness of the proposed algorithm in achieving superior diagnostic performance with a 97.54% accuracy rate.

17.
Gastric Cancer ; 27(3): 519-538, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38460015

RESUMO

BACKGROUND: Gastric cancer with peritoneal metastasis (PM-GC), recognized as one of the deadliest cancers. However, whether and how the tumor cell-extrinsic tumor microenvironment (TME) is involved in the therapeutic failure remains unknown. Thus, this study systematically assessed the immunosuppressive tumor microenvironment in ascites from patients with PM-GC, and its contribution to dissemination and immune evasion of ascites-disseminated tumor cells (aDTCs). METHODS: Sixty-three ascites and 43 peripheral blood (PB) samples from 51 patients with PM-GC were included in this study. aDTCs in ascites and circulating tumor cells (CTCs) in paired PB were immunophenotypically profiled. Using single-cell RNA transcriptional sequencing (scRNA-seq), crosstalk between aDTCs and the TME features of ascites was inspected. Further studies on the mechanism underlying aDTCs-immune cells crosstalk were performed on in vitro cultured aDTCs. RESULTS: Immune cells in ascites interact with aDTCs, prompting their immune evasion. Specifically, we found that the tumor-associated macrophages (TAMs) in ascites underwent a continuum lineage transition from cathepsinhigh (CTShigh) to complement 1qhigh (C1Qhigh) TAM. CTShigh TAM initially attracted the metastatic tumor cells to ascites, thereafter, transitioning terminally to C1Qhigh TAM to trigger overproliferation and immune escape of aDTCs. Mechanistically, we demonstrated that C1Qhigh TAMs significantly enhanced the expression of PD-L1 and NECTIN2 on aDTCs, which was driven by the activation of the C1q-mediated complement pathway. CONCLUSIONS: For the first time, we identified an immunosuppressive macrophage transition from CTShigh to C1Qhigh TAM in ascites from patients with PM-GC. This may contribute to developing potential TAM-targeted immunotherapies for PM-GC.


Assuntos
Neoplasias Peritoneais , Neoplasias Gástricas , Humanos , Neoplasias Gástricas/patologia , Macrófagos Associados a Tumor/metabolismo , Macrófagos Associados a Tumor/patologia , Ascite , Neoplasias Peritoneais/secundário , Complemento C1q , Evasão da Resposta Imune , Microambiente Tumoral
18.
Atherosclerosis ; 391: 117487, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38492245

RESUMO

BACKGROUND AND AIMS: Therapeutic arteriogenesis is a promising direction for the treatment of ischemic disease caused by atherosclerosis. However, pharmacological or biological approaches to stimulate functional collateral vessels are not yet available. Identifying new drug targets to promote and explore the underlying mechanisms for therapeutic arteriogenesis is necessary. METHODS: Peptide OM-LV20 (20 ng/kg) was administered for 7 consecutive days on rat hindlimb ischemia model, collateral vessel growth was assessed by H&E staining, liquid latex perfusion, and specific immunofluorescence. In vitro, we detected the effect of OM-LV20 on human umbilical vein endothelial cells (HUVEC) proliferation and migration. After transfection, we performed quantitative real-time polymerase chain reaction, in situ-hybridization and dual luciferase reporters to assessed effective miRNAs and target genes. The proteins related to downstream signaling pathways were detected by Western blot. RESULTS: OM-LV20 significantly increased visible collateral vessels and endothelial nitric oxide synthase (eNOS), together with enhanced inflammation cytokine and monocytes/macrophage infiltration in collateral vessels. In vitro, we defined a novel microRNA (miR-29b-3p), and its inhibition enhanced proliferation and migration of HUVEC, as well as the expression of vascular endothelial growth factor A (VEGFA). OM-LV20 also promoted migration and proliferation of HUVEC, and VEGFA expression was mediated via inhibition of miR-29b-3p. Furthermore, OM-LV20 influenced the protein levels of VEGFR2 and phosphatidylinositol3-kinase (PI3K)/AKT and eNOS in vitro and invivo. CONCLUSIONS: Our data indicated that OM-LV20 enhanced arteriogenesis via the miR-29b-3p/VEGFA/VEGFR2-PI3K/AKT/eNOS axis, and highlighte the application potential of exogenous peptide molecular probes through miRNA, which could promote effective therapeutic arteriogenesis in ischemic conditions.


Assuntos
MicroRNAs , Peptídeos , Fator A de Crescimento do Endotélio Vascular , Humanos , Ratos , Animais , Artéria Femoral/metabolismo , Proteínas Proto-Oncogênicas c-akt/metabolismo , Fosfatidilinositol 3-Quinases/metabolismo , MicroRNAs/genética , MicroRNAs/metabolismo , Células Endoteliais da Veia Umbilical Humana/metabolismo , Isquemia/genética , Proliferação de Células
19.
Heliyon ; 10(5): e26963, 2024 Mar 15.
Artigo em Inglês | MEDLINE | ID: mdl-38449661

RESUMO

Mechanical processing and operations are widely involved in modern industry. Large amount of oil mist is tended to be produced and will diffuse in the processing workshop when metalworking fluids are applied on the high temperature workpiece. The ventilation modes and air distributions can influence the air pollutants dilution in machining workshops. Therefore, this paper presents both experimental investigation and simulation study on the oil mist particles diffusion under different ventilation modes. The results identified PM2.5 as the primary component among different oil mist particles generated during a typical machining process. The distribution of oil mist particles in a full-scale machining workshop laboratory was investigated under two ventilation modes: high-sidewall nozzle air supply and low-sidewall air supply. Results revealed obvious influences of both air supply modes on the distribution of oil mist particles. Under the high-sidewall-nozzle air supply mode, the airflow and the oil mist distribution in the workshop was relatively uniform; while the low-sidewall-vent air supply mode led to an uneven distribution of oil mist particles, and the maximum oil mist concentration appeared at the height of 3 m. Under both modes, the attempts to increase the airflow rate are not always successful. Compared with low-sidewall-vent air supply mode, the high-sidewall-nozzle air supply mode presents better performance in achieving lower overall particle concentration level. Overall, the results of this study give useful reference to improve the air quality of industrial plant by properly designing the ventilation mode of machining workshop.

20.
Biomedicines ; 12(3)2024 Mar 19.
Artigo em Inglês | MEDLINE | ID: mdl-38540299

RESUMO

Periodontitis and inflammatory bowel disease (IBD) are both chronic inflammatory diseases that are characterized by abnormal host immune responses and microbiota dysbiosis. Emerging evidence implies potential associations between periodontitis and IBD. Porphyromonas gingivalis (P. gingivalis), a primary cause of periodontitis, is thought to play a role in the development of IBD through the oral-gut disease axis. However, the precise mechanisms of its involvement remain enigmatic. In this narrative review, we begin with a discussion of the bidirectional relationship between periodontitis and IBD and the involvement of P. gingivalis in each of the two diseases. Further, we summarize the possible routes by which P. gingivalis links periodontitis and IBD through the oral-gut axis, as well as the underlying mechanisms of its involvement in the pathogenesis of IBD. Collectively, P. gingivalis participates in the progression of IBD through gut dysbiosis, impairment of the intestinal barrier, release of inflammatory mediators, and disturbance of the immune response. The above findings may provide new insights for exploring novel biomarkers and potential therapeutic approaches for IBD.

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