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1.
Cell Mol Life Sci ; 81(1): 180, 2024 Apr 13.
Artigo em Inglês | MEDLINE | ID: mdl-38613672

RESUMO

Aberrant remodeling of uterine spiral arteries (SPA) is strongly associated with the pathogenesis of early-onset preeclampsia (EOPE). However, the complexities of SPA transformation remain inadequately understood. We conducted a single-cell RNA sequencing analysis of whole placental tissues derived from patients with EOPE and their corresponding controls, identified DAB2 as a key gene of interest and explored the mechanism underlying the communication between Extravillous trophoblast cells (EVTs) and decidual vascular smooth muscle cells (dVSMC) through cell models and a placenta-decidua coculture (PDC) model in vitro. DAB2 enhanced the motility and viability of HTR-8/SVneo cells. After exposure to conditioned medium (CM) from HTR-8/SVneoshNC cells, hVSMCs exhibited a rounded morphology, indicative of dedifferentiation, while CM-HTR-8/SVneoshDAB2 cells displayed a spindle-like morphology. Furthermore, the PDC model demonstrated that CM-HTR-8/SVneoshDAB2 was less conducive to vascular remodeling. Further in-depth mechanistic investigations revealed that C-X-C motif chemokine ligand 8 (CXCL8, also known as IL8) is a pivotal regulator governing the dedifferentiation of dVSMC. DAB2 expression in EVTs is critical for orchestrating the phenotypic transition and motility of dVSMC. These processes may be intricately linked to the CXCL8/PI3K/AKT pathway, underscoring its central role in intricate SPA remodeling.


Assuntos
Amarelo de Eosina-(YS)/análogos & derivados , Interleucina-8 , Fosfatidiletanolaminas , Pré-Eclâmpsia , Gravidez , Humanos , Feminino , Interleucina-8/genética , Fosfatidilinositol 3-Quinases , Pré-Eclâmpsia/genética , Placenta , Artérias , Meios de Cultivo Condicionados , Proteínas Adaptadoras de Transdução de Sinal , Proteínas Reguladoras de Apoptose
2.
Chemistry ; : e202400714, 2024 Apr 15.
Artigo em Inglês | MEDLINE | ID: mdl-38622057

RESUMO

Quantum chemical calculations using ab initio methods at the MRCI+Q(8,9)/def2-QZVPPD and CCSD(T)/def2-QZVPPD levels as well as density functional theory are reported for the diatomic molecules AeN- (Ae = Ca, Sr, Ba). The nature of the bonds is analyzed with a variety of methods. The anions CaN- and SrN- have electronic triplet (3Π) ground states with nearly identical bond dissociation energies De ~57 kcal/mol calculated at the MRCI+Q(8,9)/def2-QZVPPD level of theory. In contrast, the heavier homologue BaN- has a singlet (1Σ+) ground state, which is only 1.1 kcal/mol below the triplet (3Σ-) state. The computed bond dissociation energy of (1Σ+) BaN- is 68.4 kcal/mol. The calculations at the CCSD(T)-full/def2-QZVPPD and BP86-D3(BJ)/def2-QZVPPD levels of theory are in reasonable agreement with the MRCI+Q(8,9)/def2-QZVPPD data except for the singlet (1Σ+) state, which has a large multireference character. The calculated atomic partial charges given by the CM5, Voronoi and Hirshfeld methods suggest small to medium-sized charge donation toward Ae atom Ae←N- for most electronic states. In contrast, the NBO method predicts for all species medium to large electronic charge donation toward nitrogen Ae→N-, which is due to the neglect of the (n)p AOs of Ae atoms as genuine valence orbitals.

3.
Plant Cell Environ ; 2024 Apr 16.
Artigo em Inglês | MEDLINE | ID: mdl-38623040

RESUMO

Phytoplasmic SAP11 effectors alter host plant architecture and flowering time. However, the exact mechanisms have yet to be elucidated. Two SAP11-like effectors, SJP1 and SJP2, from 'Candidatus Phytoplasma ziziphi' induce shoot branching proliferation. Here, the transcription factor ZjTCP7 was identified as a central target of these two effectors to regulate floral transition and shoot branching. Ectopic expression of ZjTCP7 resulted in enhanced bolting and earlier flowering than did the control. Interaction and expression assays demonstrated that ZjTCP7 interacted with the ZjFT-ZjFD module, thereby enhancing the ability of these genes to directly bind to the ZjAP1 promoter. The effectors SJP1 and SJP2 unravelled the florigen activation complex by specifically destabilising ZjTCP7 and ZjFD to delay floral initiation. Moreover, the shoot branching of the ZjTCP7-SRDX transgenic Arabidopsis lines were comparable to those of the SJP1/2 lines, suggesting the involvement of ZjTCP7 in the regulation of shoot branching. ZjTCP7 interacted with the branching repressor ZjBRC1 to enhance suppression of the auxin efflux carrier ZjPIN3 expression. ZjTCP7 also directly bound to and upregulated the auxin biosynthesis gene ZjYUCCA2, thereby promoting auxin accumulation. Our findings confirm that ZjTCP7 serves as a bifunctional regulator destabilised by the effectors SJP1 and SJP2 to modulate plant development.

4.
Angew Chem Int Ed Engl ; : e202402628, 2024 Apr 16.
Artigo em Inglês | MEDLINE | ID: mdl-38623865

RESUMO

Production of thermoelectric materials from solution-processed particles involves the synthesis of particles, their purification and densification into pelletized material. Chemical changes that occur during each one of these steps render them performance determining. Particularly the purification steps, bypassed in conventional solid-state synthesis, are the cause for large discrepancies among similar solution-processed materials. In present work, the investigation focuses on a water-based surfactant free solution synthesis of SnSe, a highly relevant thermoelectric material. We show and rationalize that the number of leaching steps, purification solvent, annealing, and annealing atmosphere have significant influence on the Sn:Se ratio and impurity content in the powder. Such compositional changes that are undetectable by conventional characterization techniques lead to distinct consolidated materials with different types and concentration of defects. Additionally, the profound effect on their transport properties is demonstrated. We emphasize that understanding the chemistry and identifying key chemical species and their role throughout the process is paramount for optimizing material performance. Furthermore, we aim to demonstrate the necessity of comprehensive reporting of these steps as a standard practice to ensure material reproducibility.

5.
J Agric Food Chem ; 2024 Apr 16.
Artigo em Inglês | MEDLINE | ID: mdl-38625103

RESUMO

Phlorizin (PHZ) is one of the main pharmacologically active ingredients in Lithocarpus polystachyus. We have previously shown that PHZ inhibits the replication of bovine viral diarrhea virus (BVDV), but the exact antiviral mechanism, especially in vivo, is still unknown. Here, we further confirm that PHZ has good protective effects in BVDV-infected mice. We analyzed BVDV-induced CD3+, CD4+, and CD8+ T cells among peripheral blood lymphocytes and found that PHZ significantly restored their percentage. Metagenomic analyses revealed that PHZ markedly improved the richness and diversity of intestinal microbiota and increased the abundance of potentially health-related microbes (families Lachnosipiraceae, Ruminococcaceae, and Oscillospiraceae). Specifically, the relative abundance of short chain fatty acid (SCFA)-producing bacteria, including Lachnospiraceae_UCG-006, unclassified_f_Ruminococcaceae, Oscillibacter, Intestinimonas, Blautia, and Lachnoclostridium increased significantly after PHZ treatment. Interestingly, BVDV-infected mice that received fecal microbiota from PHZ-treated mice (PHZ-FMT) had a significantly lower viral load in the duodenum and jejunum than untreated mice. Pathological lesions of duodenum and jejunum were also greatly reduced in the PHZ-FMT group, confirming a significant antiviral effect. These findings show that gut microbiota play an important role in PHZ's antiviral activity and suggest that their targeted intervention might be a promising endogenous strategy to prevent and control BVDV.

6.
Anal Chem ; 2024 Apr 16.
Artigo em Inglês | MEDLINE | ID: mdl-38625745

RESUMO

Pathogenic bacteria significantly contribute to elevated morbidity and mortality rates, highlighting the urgent need for early and precise detection. Currently, there is a paucity of effective broad-spectrum methods for detecting pathogenic bacteria. We have developed an innovative proton-responsive series piezoelectric quartz crystal (PR-SPQC) platform for the broad-spectrum identification of pathogenic bacteria. This was achieved by retrieving and aligning sequences from the NCBI GenBank database to identify and validate 16S rRNA oligonucleotide sequences that are signatures of pathogenic bacteria but absent in humans or fungi. The hyperbranched rolling circle amplification, activated exclusively by the screened target, exponentially generates protons that are detected by SPQC through a 2D polyaniline (PANI) film. The PR-SPQC platform demonstrates broad-spectrum capabilities in detecting pathogenic bacteria, with a detection limit of 2 CFU/mL within 90 min. Clinical testing of blood samples yielded satisfactory results. With its advantages in miniaturization, cost efficiency, and suitability for point-of-care testing, PR-SPQC has the potential to be extensively used for the rapid identification of diverse pathogenic bacteria within clinical practice and public health sectors.

7.
Natl Sci Rev ; 11(4): nwae063, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38623453

RESUMO

The Chinese Bayan Obo deposit is a world-class rare earth element (REE) deposit with considerable niobium (Nb) and iron (Fe) resources. A complete genetic understanding on all metals is fundamental for establishing genetic models at Bayan Obo. With extensive research being focused on REE enrichment, the timing and controls of Nb enrichment remain unresolved at Bayan Obo, which is mainly due to the challenges in dating, i.e. multistage thermal events, fine-grained minerals with complex textures and the rare occurrence of uranium-enriched minerals with mature dating methods. Based on robust geological and petrographic frameworks, here we conducted ion probe uranium-lead (U-Pb) dating of ferrocolumbite to unravel the timing, hence the genesis of Nb mineralization. Three types of hydrothermal ferrocolumbites-key Nb-bearing minerals-are identified based on their textures and mineral assemblages. They yield U-Pb ages of 1312 ± 47 Ma (n = 99), 438 ± 7 Ma (n = 93), and 268 ± 5 Ma (n = 19), respectively. In line with deposit geology, we tentatively link the first, second and third stage Nb mineralization to Mesoproterozoic carbonatite magmatism, ubiquitous early Paleozoic hydrothermal activity, and Permian granitic magmatism, respectively. While quantifying the contribution of metal endowment from each stage requires further investigation, our new dates highlight that multi-stage mineralization is critical for Nb enrichment at Bayan Obo, which may also have implications for the enrichment mechanism of Nb in REE deposits in general.

8.
Gastroenterol Rep (Oxf) ; 12: goae031, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38628397

RESUMO

The low incidence of combined hepatocellular cholangiocarcinoma (cHCC-CCA) is an important factor limiting research progression. Our study extensively included nearly three decades of relevant literature and assembled the most comprehensive database comprising 5,742 patients with cHCC-CCA. We summarized the characteristics, tumor markers, and clinical features of these patients. Additionally, we present the evolution of cHCC-CCA classification and explain the underlying rationale for these classification standards. We reviewed cHCC-CCA diagnostic advances using imaging features, tumor markers, and postoperative pathology, as well as treatment options such as surgical, adjuvant, and immune-targeted therapies. In addition, recent advances in more effective chemotherapeutic regimens and immune-targeted therapies were explored. Furthermore, we described the molecular mutation features and potential specific markers of cHCC-CCA. The prognostic value of Nestin has been proven, and we speculate that Nestin will also play a role in classification and diagnosis. However, further research is needed. Moreover, we believe that the possibility of using machine learning liquid biopsy for preoperative diagnosis and establishing a scoring system are directions for future research.

9.
New J Chem ; 48(15): 6704-6713, 2024 Apr 15.
Artigo em Inglês | MEDLINE | ID: mdl-38628578

RESUMO

FeNbO4 sonocatalysts were successfully synthesized by a simple hydrothermal route at pH values of 3, 5, 7, 9 and 11. The catalysts were characterized by XRD, XPS, TEM, SEM, N2 adsorption and DRS to analyse the effect of pH parameters on the physicochemical properties of the materials during hydrothermal synthesis. The sonocatalytic activity of FeNbO4 microspheres was evaluated by using acid orange 7 (AO7) as the simulated contaminant. The experimental results showed that the best sonocatalytic degradation ratio (97.45%) of organic dyes could be obtained under the conditions of an initial AO7 concentration of 10 mg L-1, an ultrasonic power of 200 W, a catalyst dosage of 1.0 g L-1, and a pH of 3. Moreover, the sonocatalysts demonstrated consistent durability and stability across multiple test cycles. After active species capture experiments and calculation of the energy band, a possible mechanism was proposed based on the special Fenton-like mechanism and the dissociation of H2O2. This research shows that FeNbO4 microspheres can be used as sonocatalysts for the purification of organic wastewater, which has a promising application prospect.

10.
Front Neurosci ; 18: 1377702, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38629052

RESUMO

Purpose: The purpose of this study was to observe, using Footscan analysis, the effect of electromyographic feedback functional electrical stimulation (FES) on the changes in the plantar pressure of drop foot patients. Methods: This case-control study enrolled 34 stroke patients with foot drop. There were 17 cases received FES for 20 min per day, 5 days per week for 4 weeks (the FES group) and the other 17 cases only received basic rehabilitations (the control group). Before and after 4 weeks, the walking speed, spatiotemporal parameters and plantar pressure were measured. Results: After 4 weeks treatments, Both the FES and control groups had increased walking speed and single stance phase percentage, decreased step length symmetry index (SI), double stance phase percentage and start time of the heel after 4 weeks (p < 0.05). The increase in walking speed and decrease in step length SI in the FES group were more significant than the control group after 4 weeks (p < 0.05). The FES group had an increased initial contact phase, decreased SI of the maximal force (Max F) and impulse in the medial heel after 4 weeks (p < 0.05). Conclusion: The advantages of FES were: the improvement of gait speed, step length SI, and the enhancement of propulsion force were more significant. The initial contact phase was closer to the normal range, which implies that the control of ankle dorsiflexion was improved. The plantar dynamic parameters between the two sides of the foot were more balanced than the control group. FES is more effective than basic rehabilitations for stroke patients with foot drop based on current spatiotemporal parameters and plantar pressure results.

11.
J Leukoc Biol ; 2024 Apr 17.
Artigo em Inglês | MEDLINE | ID: mdl-38630870

RESUMO

The treatment of non-healing wounds, such as diabetic ulcers, remains a critical clinical challenge. Recent breakthroughs in cell therapy have shown great promise, with one primary focus on preparing cells with comprehensive reparative functions and foreseeable safety. In our previous study, we recapitulated the pro-regenerative and immunosuppressive functions of tumor-associated macrophages (TAMs) in non-tumor-derived macrophages, endowing the latter with characteristics for promoting diabetic wound healing - termed TAMs-educated macrophages (TAMEMs). To eliminate the use of tumor-derived sources and devise a more controllable method to prepare TAMEM-like cells, in this study, we identify a cocktail comprising five recombinant proteins as an essential condition to induce non-polarized macrophages (termed TAMEMs5) into therapeutic cells with pro-healing functions. The screened five factors are osteopontin (OPN), macrophage inflammatory protein (MIP)-2, chemokine (C-C motif) ligand 8 (CCL8), vascular endothelial growth factor (VEGF)-B, and macrophage colony-stimulating factor (M-CSF). We demonstrate the rationale for screening these factors and the phenotype of TAMEMs5 prepared from murine bone marrow-derived macrophages, which exhibit angiogenic and immunomodulatory effects in vitro. Then, we induce primary human monocytes from periphery blood into TAMEMs5, which show pro-healing effects in a human primary cell-based ex vivo model (T-SkinTM). Our study demonstrates a simple, effective, and controllable approach to induce primary macrophages to possess repairing activities, which may provide insights for developing cell-based therapeutics for non-healing wounds clinically.

13.
Artigo em Inglês | MEDLINE | ID: mdl-38609654

RESUMO

PURPOSE: Tyrosine kinase inhibitor (TKI) resistance is the main type of drug resistance in lung cancer patients with epidermal growth factor receptor (EGFR) mutations, but its underlying mechanism remains unclear. The purpose of this work was to investigate the mechanism by which PARP1 regulates EGFR-TKI resistance to identify potential targets for combating drug resistance. METHODS: The GEO databases, TCGA databases, western blot and qPCR studies were used to investigate the expression of PARP1 in lung cancer cells and tissues and its correlation with the prognosis of lung cancer. The expression of PARP1 in lung cancer TKI resistant cell PC9-ER and TKI sensitive cell PC9 was analyzed by qPCR and western blot. After knocking down of PARP1, CCK-8 assays, colony formation, flow cytometry were used to investigate its impact on erlotinib sensitivity, cell survival, cell cycle, and apoptosis. RNA-seq was used to investigate the mechanism by which PARP1 participates in EGFR-TKI resistance, and the results were validated in vitro and in vivo studies. RESULTS: PARP1 was highly expressed in both lung cancer tissues and cells. Subsequently, increased PARP1 expression was observed in PC9-ER compared with its parental cell line. Knockdown of PARP1 increased erlotinib sensitivity, promoted cell apoptosis, and suppressed cell growth. RNA-seq and previous studies have shown that the PI3K/AKT/mTOR/P70S6K pathway is involved in PARP1-mediated TKI resistance, and these results were confirmed by Western blot in vitro and in vivo. CONCLUSION: PARP1 may serve as a potential therapeutic target for reversing EGFR-TKI resistance in NSCLC via the PI3K/AKT/mTOR/P70S6K pathway.

14.
Mol Divers ; 2024 Apr 13.
Artigo em Inglês | MEDLINE | ID: mdl-38609691

RESUMO

4-Hydroxyphenylpyruvate dioxygenase (EC 1.13.11.27; HPPD) is one of the important target enzymes in the development of herbicides. To discover novel HPPD inhibitors with unique molecular, 39 cyclohexanedione derivations containing pyrazole and pyridine groups were designed and synthesized. The preliminary herbicidal activity test results showed that some compounds had obvious inhibitory effects on monocotyledon and dicotyledonous weeds. The herbicidal spectrums of the highly active compounds were further determined, and the compound G31 exhibited the best inhibitory rate over 90% against Plantago depressa Willd and Capsella bursa-pastoris at the dosages of 75.0 and 37.5 g ai/ha, which is comparable to the control herbicide mesotrione. Moreover, compound G31 showed excellent crop safety, with less than or equal to 10% injury rates to corn, sorghum, soybean and cotton at a dosage of 225 g ai/ha. Molecular docking and molecular dynamics simulation analysis revealed that the compound G31 could stably bind to Arabidopsis thaliana HPPD (AtHPPD). This study indicated that the compound G31 could be used as a lead molecular structure for the development of novel HPPD inhibitors, which provided an idea for the design of new herbicides with unique molecular scaffold.

15.
Biomed Pharmacother ; 174: 116585, 2024 Apr 13.
Artigo em Inglês | MEDLINE | ID: mdl-38615611

RESUMO

Emerging research into metabolic dysfunction-associated steatotic liver disease (MASLD) up until January 2024 has highlighted the critical role of cuproptosis, a unique cell death mechanism triggered by copper overload, in the disease's development. This connection offers new insights into MASLD's complex pathogenesis, pointing to copper accumulation as a key factor that disrupts lipid metabolism and insulin sensitivity. The identification of cuproptosis as a significant contributor to MASLD underscores the potential for targeting copper-mediated pathways for novel therapeutic approaches. This promising avenue suggests that managing copper levels could mitigate MASLD progression, offering a fresh perspective on treatment strategies. Further investigations into how cuproptosis influences MASLD are essential for unraveling the detailed mechanisms at play and for identifying effective interventions. The focus on copper's role in liver health opens up the possibility of developing targeted therapies that address the underlying causes of MASLD, moving beyond symptomatic treatment to tackle the root of the problem. The exploration of cuproptosis in the context of MASLD exemplifies the importance of understanding metal homeostasis in metabolic diseases and represents a significant step forward in the quest for more effective treatments. This research direction lights path for innovative MASLD management and reversal.

16.
Toxicon ; : 107709, 2024 Apr 12.
Artigo em Inglês | MEDLINE | ID: mdl-38615996

RESUMO

Deoxynivalenol is a widespread feed contaminant that leads to vomit, which results in serious symptom such as increased intestinal permeability and even intestinal mucosal necrosis. Recent studies have reported the role of quercetin in alleviating deoxynivalenol-induced intestinal injury; however, the mechanisms and targets remain unclear. Thus, we aimed to identify the mechanisms of action by using a combination of network pharmacology and molecular docking. We identified 151 quercetin targets, 235 deoxynivalenol targets and 47 porcine intestinal injury targets by searching compound database and PubMed database, among which there were two common targets. The PPI network showed that the key proteins involved are NQO1 and PPAR-γ. The PPI network showed that the key proteins involved were NQO1 and PPARG. GO analysis found that genes were enriched primarily in response to oxidative stress. The PPI network showed that the key proteins involved are NQO1 and PPAR-γ. The genes are enriched primarily in response to oxidative stress. KEGG analysis showed enrichment of the HIF, reactive oxygen species and other signaling pathways. The molecular docking results indicated key binding activity between NQO1-quercetin and PPAR-γ-quercetin. By using network pharmacology, we have revealed the potential molecular mechanisms by which quercetin alleviates deoxynivalenol-induced porcine intestinal injury, which lays the foundation for the development of drugs to treat deoxynivalenol-induced intestinal injury in pigs.

17.
Cancer Invest ; : 1-17, 2024 Apr 14.
Artigo em Inglês | MEDLINE | ID: mdl-38616306

RESUMO

Esophageal squamous cell carcinoma (ESCC) presents a five-year survival rate below 20%, underscoring the need for improved prognostic markers. Our study analyzed ESCC-specific datasets to identify consistently differentially expressed genes. A Venn analysis followed by gene network interactions revealed 23 key genes, from which we built a prognostic model using the COX algorithm (p = 0.000245, 3-year AUC = 0.967). This model stratifies patients into risk groups, with high-risk individuals showing worse outcomes and lower chemotherapy sensitivity. Moreover, a link between risk scores and M2 macrophage infiltration, as well as significant correlations with immune checkpoint genes (e.g., SIGLEC15, PDCD1LG2, and HVCR2), was discovered. High-risk patients had lower Tumor Immune Dysfunction and Exclusion (TIDE) values, suggesting potential responsiveness to immune checkpoint blockade (ICB) therapy. Our efficient 23-gene prognostic model for ESCC indicates a dual utility in assessing prognosis and guiding therapeutic decisions, particularly in the context of ICB therapy for high-risk patients.

18.
J Anal Toxicol ; 2024 Mar 29.
Artigo em Inglês | MEDLINE | ID: mdl-38619371

RESUMO

Since the 2000s, an increasing number of new psychoactive substances have appeared on the illicit drug market. ß-keto-arylcyclohexylamine compounds play important pharmacological roles in anesthesia; however, because these new psychoactive substances have rapidly increasing illicit recreational use, the lack of detailed toxicity data are of particular concern. Therefore, analysis of their metabolites can help forensic personnel provide references and suggestions on whether a suspect has taken an illicit new psychoactive ß-keto-arylcyclohexylamine. The present study investigated the in vitro and in vivo metabolism and metabolites of three ß-keto-arylcyclohexylamines: deschloro-N-ethyl-ketamine, fluoro-N-ethyl-ketamine and bromoketamine. In vitro and in vivo models were established using zebrafish and human liver microsomes for analysis of Phase I and Phase II metabolites by liquid chromatography-high-resolution mass spectrometry. Altogether, 49 metabolites were identified. The results were applied for the subject urine samples of known fluoro-N-ethyl-ketamine consumer screen analysis in forensic cases. Hydroxy-deschloro-N-ethyl-ketamine, hydroxy-fluoro-N-ethyl-ketamine and hydroxy-bromoketamine were recommended as potential biomarkers for documenting intake in clinical and forensic cases.

19.
Chem Commun (Camb) ; 2024 Apr 15.
Artigo em Inglês | MEDLINE | ID: mdl-38619398

RESUMO

A convenient method for oxidant-promoted radical cascade acylation or decarbonylative alkylation of 1,7-dienes with aldehydes has been established. This method allows for the rapid construction of N-containing polycyclic skeletons in a highly regio- and stereoselective manner. This transformation provides a simple and efficient method for the preparation of a range of tetrahydro-6H-indeno[2,1-c]quinolinone derivatives by sequential formation of three new carbon-carbon bonds. Additionally, this radical cascade cyclization can selectively convert aldehydes into aroyl/primary aliphatic acyl radicals and secondary or tertiary alkyl radicals.

20.
Biomed Pharmacother ; 174: 116572, 2024 Apr 15.
Artigo em Inglês | MEDLINE | ID: mdl-38626519

RESUMO

Epigenetic regulation and mitochondrial dysfunction are essential to the progression of idiopathic pulmonary fibrosis (IPF). Curcumin (CCM) in inhibits the progression of pulmonary fibrosis by regulating the expression of specific miRNAs and pulmonary fibroblast mitochondrial function; however, the underlying mechanism is unclear. C57BL/6 mice were intratracheally injected with bleomycin (5 mg/kg) and treated with CCM (25 mg/kg body weight/3 times per week, intraperitoneal injection) for 28 days. Verhoeff-Van Gieson, Picro sirius red, and Masson's trichrome staining were used to examine the expression and distribution of collagen and elastic fibers in the lung tissue. Pulmonary fibrosis was determined using micro-computed tomography and transmission electron microscopy. Human pulmonary fibroblasts were transfected with miR-29a-3p, and RT-qPCR, immunostaining, and western blotting were performed to determine the expression of DNMT3A and extracellular matrix collagen-1 (COL1A1) and fibronectin-1 (FN1) levels. The expression of mitochondrial electron transport chain complex (MRC) and mitochondrial function were detected using western blotting and Seahorse XFp Technology. CCM in increased the expression of miR-29a-3p in the lung tissue and inhibited the DNMT3A to reduce the COL1A1 and FN1 levels leading to pulmonary extracellular matrix remodeling. In addition, CCM inhibited pulmonary fibroblasts MRC and mitochondrial function via the miR-29a-3p/DNMT3A pathway. CCM attenuates pulmonary fibrosis via the miR-29a-3p/DNMT3A axis to regulate extracellular matrix remodeling and mitochondrial function and may provide a new therapeutic intervention for preventing pulmonary fibrosis.

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