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1.
J Med Chem ; 2024 Apr 17.
Artigo em Inglês | MEDLINE | ID: mdl-38630077

RESUMO

Multitarget medications represent an appealing therapy against the disease with multifactorial abnormalities─cancer. Therefore, simultaneously targeting son of sevenless 1 (SOS1) and epidermal growth factor receptor (EGFR), two aberrantly expressed proteins crucial for the oncogenesis and progression of prostate cancer, may achieve active antitumor effects. Here, we discovered dual SOS1/EGFR-targeting compounds via pharmacophore-based docking screening. The most prominent compound SE-9 exhibited nanomolar inhibition activity against both SOS1 and EGFR and efficiently suppressed the phosphorylation of ERK and AKT in prostate cancer cells PC-3. Cellular assays also revealed that SE-9 displayed strong antiproliferative activities through diverse mechanisms, such as induction of cell apoptosis and G1 phase cell cycle arrest, as well as reduction of angiogenesis and migration. Further in vivo findings showed that SE-9 potently inhibited tumor growth in PC-3 xenografts without obvious toxicity. Overall, SE-9 is a novel dual-targeting SOS1/EGFR inhibitor that represents a promising treatment strategy for prostate cancer.

2.
J Med Chem ; 2024 Apr 17.
Artigo em Inglês | MEDLINE | ID: mdl-38630440

RESUMO

An efficient protocol for the synthesis of ß-trifluoroethoxydimethyl selenides was achieved under mild reaction conditions, and 39 compounds were prepared. All compounds were evaluated for their abilities to inhibit RANKL-induced osteoclastogenesis, compound 4aa exhibited the most potent activity. Further investigations revealed that 4aa could inhibit F-actin ring generation, bone resorption, and osteoclast-specific gene expression in vitro. Western blot analyses demonstrated that compound 4aa abrogated the RANKL-induced mitogen-activated protein kinase and NF-kB-signaling pathways. In addition, 4aa also displayed a notable impact on the osteoblastogenesis of MC3T3-E1 preosteoblasts. In vivo experiments revealed that compound 4aa significantly ameliorated bone loss in an ovariectomized (OVX) mice model. Furthermore, the surface plasmon resonance experiment results revealed that 4aa probably bound to RANKL. Collectively, the above-mentioned findings suggested that compound 4aa as a potential RANKL inhibitor averted OVX-triggered osteoporosis by regulating the inhibition of osteoclast differentiation and stimulation of osteoblast differentiation.

3.
Comput Struct Biotechnol J ; 23: 1534-1546, 2024 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-38633388

RESUMO

Glioblastoma (GBM) is one of the most malignant tumors of the central nervous system. The pattern of immune checkpoint expression in GBM remains largely unknown. We performed snRNA-Seq and spatial transcriptomic (ST) analyses on untreated GBM samples. 8 major cell types were found in both tumor and adjacent normal tissues, with variations in infiltration grade. Neoplastic cells_6 was identified in malignant cells with high expression of invasion and proliferator-related genes, and analyzed its interactions with microglia, MDM cells and T cells. Significant alterations in ligand-receptor interactions were observed, particularly between Neoplastic cells_6 and microglia, and found prominent expression of VISTA/VSIG3, suggesting a potential mechanism for evading immune system attacks. High expression of TIM-3, VISTA, PSGL-1 and VSIG-3 with similar expression patterns in GBM, may have potential as therapeutic targets. The prognostic value of VISTA expression was cross-validated in 180 glioma patients, and it was observed that patients with high VISTA expression had a poorer prognosis. In addition, multimodal cross analysis integrated SnRNA-seq and ST, revealing complex intracellular communication and mapping the GBM tumor microenvironment. This study reveals novel molecular characteristics of GBM, co-expression of immune checkpoints, and potential therapeutic targets, contributing to improving the understanding and treatment of GBM.

4.
Front Psychol ; 15: 1344185, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38633878

RESUMO

Introduction: Nurses caring for patients with gynecological cancer experience significant job stress, which adversely impacts their mental health. Previous studies have indicated that perceived professional benefits serves as a protective factor for nurses' mental health, and factors such as job stress, perceived social support and self-efficacy influence their perceived professional benefits. However, the relationships between these factors and the associated mechanisms have remained incompletely understood. This study explored the role of perceived social support and self-efficacy in job stress and perceived professional benefits among nurses caring for patients with gynecological cancer. Methods: During June and July 2023, an investigation was conducted in Anhui Province. The Nurse Job Stressors Scale, Perceived Social Support Scale, Nurses' Perceived Professional Benefits Questionnaire and General Self-Efficacy Scale were administered to 311 nurses caring for patients with gynecological cancer. A chained-mediated effect model was constructed and validated. Results: Job stress negatively affected nurses' perceived professional benefits. Perceived social support was a mediator in job stress and nurses' perceived professional benefits, with a mediating effect value of -0.093. Additionally, perceived social support and self-efficacy functioned as sequential mediators in this relationship, with a mediating effect value of -0.032. Conclusion: This study unveils the influencing mechanisms of job stress on perceived professional benefits of nurses caring for patients with gynecological cancer. It is essential for nursing managers to alleviate nurses' job stress, provide sufficient and effective social support and improve their self-efficacy, ultimately enhancing their perceived professional benefits.

5.
Langmuir ; 2024 Apr 12.
Artigo em Inglês | MEDLINE | ID: mdl-38607689

RESUMO

This work aims to enhance the adsorption performance of Laponite @diatomite for organic pollutants by modifying it with cetyltrimethylammonium bromide (CTAB). The microstructure and morphology of the CTAB-modified Laponite @diatomite material were characterized using SEM, XRD, FTIR, BET, and TG. Furthermore, the influences of key parameters, containing pH, adsorbent dosage, reaction time, and reaction temperature, on the adsorption process were investigated. The kinetics, thermodynamics, and isotherm models of the adsorption process were analyzed. Finally, potential adsorption mechanisms were given based on the characterization. The research findings indicate that CTAB-La@D exhibits good adsorption performance toward Congo red (CR) over a broad pH range. The maximum adsorption capacity of CR was 451.1 mg/g under the optimum conditions (dosage = 10 mg, contact time = 240 min, initial CR concentration = 100 mg/L, temperature = 25 °C, and pH = 7). The adsorption process conformed to the pseudo-second-order kinetic model, and the adsorption isotherms indicated that the adsorption process of CR was more in line with the Langmuir model, and it was physical adsorption. Thermodynamic analysis illustrates that the adsorption process is exothermic and spontaneous. Additionally, the mechanisms of electrostatic adsorption and hydrophobic effect adsorption of CR were investigated through XPS and FTIR analysis. This work provides an effective pathway for designing high-performance adsorbents for the removal of organic dye, and the synthesized materials hold great capability for practical utilization in the treatment of wastewater.

6.
Midwifery ; 133: 103994, 2024 Apr 11.
Artigo em Inglês | MEDLINE | ID: mdl-38608543

RESUMO

BACKGROUND: Women undergoing caesarean section (CS) experience difficulties when preparing for discharge, and readiness for hospital discharge (RHD) may depend on individual characteristics. OBJECTIVE: To explore the status of RHD in women with CS, identify the latent classes of RHD, and analyse predictors from a bio-psycho-social perspective. METHODS: A sample of 410 women with CS completed the following questionnaires on demographic and obstetric characteristics: Readiness for Hospital Discharge Study-New Mother Form (RHDS-NMF), Parents' Postnatal Sense of Security (PPSS), Quality of Discharge Teaching Scale (OB-QDTS), and Postpartum Support Questionnaire (PSQ). Latent profile analysis was used to identify the latent classes of RHD. Multiple logistic regression analysis was used to analyse the predictors. RESULTS: In total, 96.6 % of women with CS reported discharge ready, and the score of RHDS-NMF was 136.09 ± 25.59. Three latent classes were identified as Low RHD (16.1 %), Moderate RHD (41.7 %), and High RHD (42.2 %). Primiparas (OR = 2.867 / 1.773; P = 0.012 / 0.033), emergency CS (OR = 3.134 / 2.470; P = 0.006 / 0.002), lower levels of PPSS (OR = 0.909 / 0.942; P = 0.009 / 0.013) and OB-ODTS (OR = 0.948 / 0.975; P < 0.001) were associated with Moderate and Low RHD. Lower PSQ predicted a higher probability of Low RHD (OR = 0.955; P = 0.038). CONCLUSIONS: The perception of RHD by women in the study was inaccurate, with more than half not being classified as High RHD. Healthcare professionals can anticipate interventions for maternal well-being based on the characteristics of the different RHD classes.

7.
Plant Dis ; : PDIS09231722RE, 2024 Apr 12.
Artigo em Inglês | MEDLINE | ID: mdl-38613135

RESUMO

Bacterial wilt caused by Ralstonia solanacearum (RS) is one of the most devastating diseases in patchouli (Pogostemon cablin [Blanco] Benth.), which results in low yield and quality of patchouli. However, no stable and effective control methods have been developed yet. To evaluate the potential of dominant bacterial endophytes in biocontrol, the endophytic bacterial diversity of patchouli was investigated based on Illumina sequencing analysis, and the ability of isolates belonging to the dominant bacterial genera to control RS wilt of patchouli was explored in pot experiments. A total of 245 bacterial genera were detected in patchouli plants, with the highest relative abundance of operational taxonomic units belonging to the genus Pseudomonas detected in roots, leaves, and stems. The Pseudomonas isolates S02, S09, and S26 showed antagonistic activity against RS in vitro and displayed many plant growth-promoting characteristics, including production of indole-3-acetic acid, siderophores, and 1-aminocyclopropane-1-carboxylic acid deaminase and phosphate- and potassium-solubilizing capability. Inoculation of patchouli plants with the isolates S02, S09, and S26 significantly improved shoot growth and decreased the incidence of bacterial wilt caused by RS. The results suggest that screening of dominant bacterial endophytes for effective biocontrol agents based on Illumina sequencing analysis is more efficient than random isolation and screening procedures.

8.
Heliyon ; 10(8): e28787, 2024 Apr 30.
Artigo em Inglês | MEDLINE | ID: mdl-38628705

RESUMO

Genetic diseases are currently diagnosed by functional mutations. However, only some mutations are associated with disease. It is necessary to establish a quick prediction model for clinical screening. Pathogenic mutations in NGLY1 cause a rare autosomal recessive disease known as congenital disorder of deglycosylation (NGLY1-CDDG). Although NGLY1-CDDG can be diagnosed through gene sequencing, clinical relevance of a detected mutation in NGLY1 needs to be further confirmed. In this study, taken NGLY1-CDDG as an example, a comprehensive and practical predictive model for pathogenic mutations on NGLY1 through an NGLY1/Glycopeptide complex model was constructed, the binding sites of NGLY1 and glycopeptides were simulated, and an in vitro enzymatic assay system was established to facilitate quick clinical decisions for NGLY1-CDDG patients. The docking model covers 42 % of reported NGLY1-CDDG missense mutations (5/12). All reported mutations were subjected to in vitro enzymatic assay in which 18 mutations were dysfunctional (18/30). In addition, a full spectrum of functional R328 mutations was assayed and 11 mutations were dysfunctional (11/19). In this study, a model of NGLY1 and glycopeptides was built for potential functional mutations in NGLY1. In addition, the effect of potential regulatory compounds, including N-acetyl-l-cysteine and dithiothreitol, on NGLY1 was examined. The established in vitro assay may serve as a standard protocol to facilitate rapid diagnosis of all mutations in NGLY1-CDDG. This method could also be applied as a comprehensive and practical predictive model for the other rare genetic diseases.

9.
Sci Rep ; 14(1): 8630, 2024 04 15.
Artigo em Inglês | MEDLINE | ID: mdl-38622211

RESUMO

Glycogen storage disease type Ib (GSD-Ib) is a rare inborn error of glycogen metabolism caused by mutations in SLC37A4. Patients with GSD-Ib are at high risk of developing inflammatory bowel disease (IBD). We evaluated the efficacy of empagliflozin, a renal sodium‒glucose cotransporter protein 2 (SGLT2) inhibitor, on colonic mucosal healing in patients with GSD-associated IBD. A prospective, single-arm, open-label clinical trial enrolled eight patients with GSD-associated IBD from Guangdong Provincial People's Hospital in China from July 1, 2022 through December 31, 2023. Eight patients were enrolled with a mean age of 10.34 ± 2.61 years. Four male and four female. The endoscopic features included deep and large circular ulcers, inflammatory hyperplasia, obstruction and stenosis. The SES-CD score significantly decreased at week 48 compared with before empagliflozin. Six patients completed 48 weeks of empagliflozin therapy and endoscopy showed significant improvement or healing of mucosal ulcers, inflammatory hyperplasia, stenosis, and obstruction. One patient had severe sweating that required rehydration and developed a urinary tract infection. No serious or life-threatening adverse events. This study suggested that empagliflozin may promote colonic mucosal healing and reduce hyperplasia, stenosis, and obstruction in children with GSD-associated IBD.


Assuntos
Compostos Benzidrílicos , Glucosídeos , Doença de Depósito de Glicogênio Tipo I , Doenças Inflamatórias Intestinais , Criança , Humanos , Masculino , Feminino , Adolescente , Constrição Patológica/complicações , Úlcera , Hiperplasia , Estudos Prospectivos , Doenças Inflamatórias Intestinais/complicações , Doenças Inflamatórias Intestinais/tratamento farmacológico , Doenças Inflamatórias Intestinais/genética , Doença de Depósito de Glicogênio Tipo I/complicações , Doença de Depósito de Glicogênio Tipo I/tratamento farmacológico , Doença de Depósito de Glicogênio Tipo I/genética , Proteínas de Transporte de Monossacarídeos/genética , Antiporters/genética
10.
J Environ Manage ; 358: 120821, 2024 Apr 09.
Artigo em Inglês | MEDLINE | ID: mdl-38599087

RESUMO

In electroplating sludge, iron (Fe) and aluminum (Al) are common impurities that need to be separated before recycling valuable heavy metals. However, the traditional Fe/Al separation process often leads to significant losses of heavy metals. To address this issue, a new approach was developed to sequentially separate Fe/Al and recycle chromium (Cr) and nickel (Ni) from real electroplating sludge. The sludge contained 4.5% Cr, 1.2% Al, 1.1% Ni, and 14.6% Fe. Initially, the sludge was completely dissolved in a mixture of hydrochloric and nitric acids. The resulting acid solution was then heated to 160 °C for 10 h with the addition of saccharose. This hydrothermal treatment led to the hydrolysis and crystallization of 98.3% of Fe, 31.8% of Cr, 1.1% of Al, and 4.9% of Ni, forming akaganeite-bearing particles. It was observed that the excessive amount of saccharose also improved the removal of Cr, Al, and Ni, but decreased the removal of Fe. After the hydrothermal treatment, the remaining supernatant was adjusted to different pH levels (1.9, 2.9, and 4.5, respectively), and then Al, Cr, and Ni were stepwise extracted using di-(2-ethylhexyl) phosphate acid (P204). The recycling efficiencies achieved were 97.4% for Al, 61.2% for Cr, and 89.3% for Ni. This approach provides a promising method for the stepwise separation of Fe/Al and the recycling of heavy metals from electroplating sludge.

11.
J Neurogastroenterol Motil ; 30(2): 143-155, 2024 Apr 30.
Artigo em Inglês | MEDLINE | ID: mdl-38576367

RESUMO

Diabetic gastroparesis (DGP) is a common complication of diabetes mellitus, marked by gastrointestinal motility disorder, a delayed gastric emptying present in the absence of mechanical obstruction. Clinical manifestations include postprandial fullness and epigastric discomfort, bloating, nausea, and vomiting. DGP may significantly affect the quality of life and productivity of patients. Research on the relationship between gastrointestinal dynamics and DGP has received much attention because of the increasing prevalence of DGP. Gastrointestinal motility disorders are closely related to a variety of factors including the absence and destruction of interstitial cells of Cajal, abnormalities in the neuro-endocrine system and hormone levels. Therefore, this study will review recent literature on the mechanisms of DGP and gastrointestinal motility disorders as well as the development of prokinetic treatment of gastrointestinal motility disorders in order to give future research directions and identify treatment strategies for DGP.

12.
Curr Pharm Des ; 2024 Apr 08.
Artigo em Inglês | MEDLINE | ID: mdl-38616754

RESUMO

BACKGROUND: Traditional Chinese medicine Scutellaria Baicalensis (SB), one of the clinical firstline heat-clearing drugs, has obvious symptomatic advantages for hepatic fibrosis with dampness-heat stasis as its syndrome. We aim to predict and validate the potential mechanism of Scutellaria baicalensis active ingredients against liver fibrosis more scientifically and effectively. METHODS: The underlying mechanism of Scutellaria baicalensis in inhibiting hepatic fibrosis was studied by applying network pharmacology, molecular docking and molecular dynamics simulation. Expression levels of markers in activated Hepatic Stellate Cells (HSC) after administration of three Scutellaria baicalensis extracts were determined by Western blot and Real-time PCR, respectively, in order to verify the anti-fibrosis effect of the active ingredients Results: There are 164 common targets of drugs and diseases screened and 115 signaling pathways obtained, which were mainly associated with protein phosphorylation, senescence and negative regulation of the apoptotic process. Western blot and Real-time PCR showed that Scutellaria baicalensis extracts could reduce the expression of HSC activation markers, and Oroxylin A had the strongest inhibitory effect on it. Molecular docking results showed that Oroxylin A had high binding activity to target proteins. Molecular dynamics simulation demonstrates promising stability of the Oroxylin A-AKT1 complex over the simulated MD time of 200 ns. CONCLUSION: Scutellaria baicalensis active ingredients may inhibit HSC proliferation, reduce the generation of pro-inflammatory factors and block the anti-inflammatory effect of inflammatory signal transduction by inducing HSC apoptosis and senescence, thus achieving the effect of anti-fibrosis.

13.
Bioorg Chem ; 146: 107320, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38569323

RESUMO

Spleen tyrosine kinase (Syk) plays a crucial role as a target for allergy treatment due to its involvement in immunoreceptor signaling. The purpose of this study was to identify natural inhibitors of Syk and assess their effects on the IgE-mediated allergic response in mast cells and ICR mice. A list of eight compounds was selected based on pharmacophore and molecular docking, showing potential inhibitory effects through virtual screening. Among these compounds, sophoraflavanone G (SFG) was found to inhibit Syk activity in an enzymatic assay, with an IC50 value of 2.2 µM. To investigate the conformational dynamics of the SYK-SFG system, we performed molecular dynamics simulations. The stability of the binding between SFG and Syk was evaluated using root mean square deviation (RMSD) and root mean square fluctuation (RMSF). In RBL-2H3 cells, SFG demonstrated a dose-dependent suppression of IgE/BSA-induced mast cell degranulation, with no significant cytotoxicity observed at concentrations below 10.0 µM within 24 h. Furthermore, SFG reduced the production of TNF-α and IL-4 in RBL-2H3 cells. Mechanistic investigations revealed that SFG inhibited downstream signaling proteins, including phospholipase Cγ1 (PLCγ1), as well as mitogen-activated protein kinases (AKT, Erk1/2, p38, and JNK), in mast cells in a dose-dependent manner. Passive cutaneous anaphylaxis (PCA) experiments demonstrated that SFG could reduce ear swelling, mast cell degranulation, and the expression of COX-2 and IL-4. Overall, our findings identify naturally occurring SFG as a direct inhibitor of Syk that effectively suppresses mast cell degranulation both in vitro and in vivo.


Assuntos
Interleucina-4 , Mastócitos , Camundongos , Animais , Interleucina-4/metabolismo , Interleucina-4/farmacologia , Mastócitos/metabolismo , Anafilaxia Cutânea Passiva , Simulação de Acoplamento Molecular , Imunoglobulina E/metabolismo , Imunoglobulina E/farmacologia , Camundongos Endogâmicos ICR , Camundongos Endogâmicos BALB C
14.
Small ; : e2311725, 2024 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-38558506

RESUMO

Photocatalytic hydrogen production is a prevalent method for hydrogen synthesis. However, high recombination rate of photogenerated carriers and high activation energy barrier of H remain persistent challenge. Here, the two-step hydrothermal method is utilized to prepare dual S-defect mediated catalyst molybdenum sulfide/zinc indium sulfide (MSv/ZISv), which has high hydrogen production rate of 8.83 mmol g-1h-1 under simulated sunlight. The achieved rate is 21.91 times higher than pure ZnIn2S4 substrate. Defects in ZIS within MSv/ZISv modify the primitive electronic structure by creating defect state that retaining good reducing power, leading to the rapid separation of electron-hole pairs and the generation of additional photogenerated carriers. The internal electric field further enhances the migration toward to cocatalyst. Simultaneously, the defects introduced on the MoS2 cause electron rearrangement, leading to electron clustering on both S vacancies and edge S. Thereby MSv/ZISv exhibits the lowest activation energy barrier and |ΔGH*|. This work explores the division of synergies between different types of S defects, providing new insights into the coupling of defect engineering.

15.
Heliyon ; 10(6): e27350, 2024 Mar 30.
Artigo em Inglês | MEDLINE | ID: mdl-38496903

RESUMO

Peripheral nerve remodeling and sensitization are involved in cancer-related bone pain. As a member of the transforming growth factor-ß class, bone morphogenetic protein 2 (BMP2) is recognized to have a role in the development of the neurological and skeletal systems. Our previous work showed that BMP2 is critical for bone cancer pain (BCP) sensitization. However, the mechanism remains unknown. In the current study, we demonstrated a substantial increase in BMP2 expression in the dorsal root ganglia (DRG) in a rat model of BCP. Knockdown of BMP2 expression ameliorated BCP in rats. Furthermore, the DRG neurons of rats with BCP expressed higher levels of calcitonin gene-related peptide (CGRP), and BCP was successfully suppressed by intrathecal injection of a CGRP receptor blocker (CGRP8-37). Downregulation of BMP2 expression reduced the expression of CGRP in the DRG of rats with BCP and relieved pain behavior. Moreover, we revealed that upregulation of CGRP expression in the DRG may be induced by activation of the BMPR/Smad1 signaling pathway. These findings suggest that BMP2 contributes to BCP by upregulating CGRP in DRG neurons via activating BMPR/Smad1 signaling pathway and that therapeutic targeting of the BMP2-Smad1-CGRP pathway may ameliorate BCP in the context of advanced cancer.

16.
BMJ Open ; 14(3): e075138, 2024 Mar 15.
Artigo em Inglês | MEDLINE | ID: mdl-38490657

RESUMO

INTRODUCTION: Alport syndrome (AS) is one of the most common fatal hereditary renal diseases in human, with a high risk of progressing to end-stage renal disease without effective treatments. Mesenchymal stem cells (MSCs) have recently emerged as a promising therapeutic strategy for chronic kidney disease. However, the safety and therapeutic potential of MSC transfusion for patients with AS are still need to be confirmed. Therefore, we have designed a clinical trial to evaluate the hypothesis that intravenous infusion of human umbilical cord-derived MSC (hUC-MSC) is safe, feasible, and well-tolerated in children with AS. METHODS AND ANALYSIS: We report the protocol of the first prospective, open-label, single-arm clinical trial to evaluate the safety and preliminary efficacy of hUC-MSC transfusion in children with early-stage AS. Paediatric patients diagnosed with AS who have persistent albuminuria will be candidates for screening. Twelve eligible patients are planned to recruit and will receive hUC-MSC infusions under close safety monitoring, and complete the efficacy assessments at scheduled follow-up visits. The primary endpoints include the occurrence of adverse events to assess safety and the albuminuria level for efficacy evaluation. Secondary endpoint assessments are based on haematuria and glomerular filtration measurements. Each patient's efficacy endpoints will be evaluated against their baseline levels. Additionally, the underlying mechanism of hUC-MSC therapy will be explored through transcriptomic and proteomic analysis of blood and urine samples. ETHICS AND DISSEMINATION: The protocol (V.1.0, date 17 January 2015) was approved by the institutional review board of the Affiliated Taihe Hospital of Hubei University of Medicine (ethical approval 03 March 2015). Written informed consent will be obtained from the patient and/or guardians before study specific process. In addition to publication in a peer-reviewed scientific journal, a lay summary of study will be available for participants and the public on the Chinese Organization for Rare Disorders website (http://www.cord.org.cn/). TRIAL REGISTRATION NUMBER: ISRCTN62094626.


Assuntos
COVID-19 , Transplante de Células-Tronco Mesenquimais , Células-Tronco Mesenquimais , Nefrite Hereditária , Humanos , Criança , SARS-CoV-2 , Nefrite Hereditária/complicações , Nefrite Hereditária/terapia , Albuminúria , Estudos Prospectivos , Proteômica , Resultado do Tratamento , Células-Tronco Mesenquimais/fisiologia , Cordão Umbilical
17.
ACS Nano ; 18(11): 7688-7710, 2024 Mar 19.
Artigo em Inglês | MEDLINE | ID: mdl-38436232

RESUMO

Extracellular matrix (ECM) remodeling is accompanied by the continuous synthesis and degradation of the ECM components. This dynamic process plays an important role in guiding cell adhesion, migration, proliferation, and differentiation, as well as in tissue development, body repair, and maintenance of homeostasis. Nanomaterials, due to their photoelectric and catalytic properties and special structure, have garnered much attention in biomedical fields for use in processes such as tissue engineering and disease treatment. Nanomaterials can reshape the cell microenvironment by changing the synthesis and degradation of ECM-related proteins, thereby indirectly changing the behavior of the surrounding cells. This review focuses on the regulatory role of nanomaterials in the process of cell synthesis of different ECM-related proteins and extracellular protease. We discuss influencing factors and possible related mechanisms of nanomaterials in ECM remodeling, which may provide different insights into the design and development of nanomaterials for the treatment of ECM disorder-related diseases.


Assuntos
Matriz Extracelular , Nanoestruturas , Matriz Extracelular/metabolismo , Proteínas da Matriz Extracelular/análise , Proteínas da Matriz Extracelular/química , Proteínas da Matriz Extracelular/metabolismo , Engenharia Tecidual , Adesão Celular
18.
Heliyon ; 10(4): e26739, 2024 Feb 29.
Artigo em Inglês | MEDLINE | ID: mdl-38434027

RESUMO

The biological mechanism of action of platelet-rich plasma (PRP) in the treatment of temporomandibular joint (TMJ) osteoarthritis remains unclear. This study explored the mechanisms underlying interleukin (IL)-1ß-induced inflammation and investigated the effect of PRP on TMJ condylar chondrocytes. Primary chondrocytes were isolated from the TMJ condyle of 4-week-old rats, and differentially expressed genes among three treatment groups (phosphate-buffered saline [control], IL-1ß, and IL-1ß + PRP) were identified using RNA-seq and characterized using Gene Ontology and Kyoto Encyclopedia of Genes and Genomes path-enrichment analyses. IL-1ß caused inflammatory injury to chondrocytes by upregulating the TNF, NF-κB, and IL-17 signaling pathways and downregulating the MAPK and PI3K/Akt signaling pathways. PRP activated the MAPK and PI3K/Akt signaling pathways, exerting a protective effect on IL-1ß-induced chondrocytes. PRP also activated the TNF and IL-17 signaling pathways, producing an inflammatory effect. Additionally, PRP increased the mRNA expression of the matrix catabolism-related genes Mmp3, Mmp9, and Mmp13; the proliferative markers Mki67 and PCNA; and the anti-apoptotic genes of the Bcl-2 family (Bcl2a1 and Bok), while reducing the expression of the pro-apoptotic genes Casp4 and Casp12. The findings suggest that the protective effect of PRP on IL-1ß-induced chondrocyte injury is mainly achieved via MAPK-PI3K/Akt signaling, increasing cell proliferation and inhibiting cell apoptosis.

20.
Bioeng Transl Med ; 9(2): e10620, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38435824

RESUMO

Skin wound healing often leads to scar formation, presenting physical and psychological challenges for patients. Advancements in messenger RNA (mRNA) modifications offer a potential solution for pulsatile cytokine delivery to create a favorable wound-healing microenvironment, thereby preventing cutaneous fibrosis. This study aimed to investigate the effectiveness of human adipose-derived stem cells (hADSCs) enriched with N 1-methylpseudouridine (m1ψ) modified transforming growth factor-ß3 (TGF-ß3) and interleukin-10 (IL-10) mRNA in promoting scar-free healing in preclinical models. The results demonstrated that the modified mRNA (modRNA)-loaded hADSCs efficiently and temporarily secreted TGF-ß3 and IL-10 proteins. In a dorsal injury model, hADSCs loaded with modRNA TGF-ß3 and IL-10 exhibited multidimensional therapeutic effects, including improved collagen deposition, extracellular matrix organization, and neovascularization. In vitro experiments confirmed the ability of these cells to markedly inhibit the proliferation and migration of keloid fibroblasts, and reverse the myofibroblast phenotype. Finally, collagen degradation mediated by matrix metalloproteinase upregulation was observed in an ex vivo keloid explant culture model. In conclusion, the synergistic effects of the modRNA TGF-ß3, IL-10, and hADSCs hold promise for establishing a scar-free wound-healing microenvironment, representing a robust foundation for the management of wounds in populations susceptible to scar formation.

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