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1.
Front Pharmacol ; 15: 1396975, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38725666

RESUMO

Osteosarcoma (OS) is the most common primary malignant bone tumor. In the clinic, usual strategies for OS treatment include surgery, chemotherapy, and radiation. However, all of these therapies have complications that cannot be ignored. Therefore, the search for better OS treatments is urgent. Black phosphorus (BP), a rising star of 2D inorganic nanoparticles, has shown excellent results in OS therapy due to its outstanding photothermal, photodynamic, biodegradable and biocompatible properties. This review aims to present current advances in the use of BP nanoparticles in OS therapy, including the synthesis of BP nanoparticles, properties of BP nanoparticles, types of BP nanoparticles, and modification strategies for BP nanoparticles. In addition, we have discussed comprehensively the application of BP in OS therapy, including single, dual, and multimodal synergistic OS therapies, as well as studies about bone regeneration and antibacterial properties. Finally, we have summarized the conclusions, limitations and perspectives of BP nanoparticles for OS therapy.

2.
Artigo em Inglês | MEDLINE | ID: mdl-38738757

RESUMO

The development of therapeutics with high antimicrobial activity and immunomodulatory effects is urgently needed for the treatment of infected wounds due to the increasing danger posed by recalcitrant-infected wounds. In this study, we developed light-controlled antibacterial, photothermal, and immunomodulatory biomimetic N/hPDA@M nanoparticles (NPs). This nanoplatform was developed by loading flavonoid naringenin onto hollow mesoporous polydopamine NPs in a π-π-stacked configuration and encasing them with macrophage membranes. First, our N/hPDA@M NPs efficiently neutralized inflammatory factors present within the wound microenvironment by the integration of macrophage membranes. Afterward, the N/hPDA@M NPs effectively dismantled bacterial biofilms through a combination of the photothermal properties of PDA and the quorum sensing inhibitory effects of naringenin. It is worth noting that N/hPDA@M NPs near-infrared-enhanced release of naringenin exhibited specificity toward the NF-κB-signaling pathway, effectively mitigating the inflammatory response. This innovative design not only conferred remarkable antibacterial properties upon the N/hPDA@M NPs but also endowed them with the capacity to modulate inflammatory responses, curbing excessive inflammation and steering macrophage polarization toward the M2 phenotype. As a result, this multifaceted approach significantly contributes to expediting the healing process of infected skin wounds.

3.
Int J Mol Sci ; 25(9)2024 Apr 25.
Artigo em Inglês | MEDLINE | ID: mdl-38731920

RESUMO

Expansins, a class of cell-wall-loosening proteins that regulate plant growth and stress resistance, have been studied in a variety of plant species. However, little is known about the Expansins present in alfalfa (Medicago sativa L.) due to the complexity of its tetraploidy. Based on the alfalfa (cultivar "XinjiangDaye") reference genome, we identified 168 Expansin members (MsEXPs). Phylogenetic analysis showed that MsEXPs consist of four subfamilies: MsEXPAs (123), MsEXPBs (25), MsEXLAs (2), and MsEXLBs (18). MsEXPAs, which account for 73.2% of MsEXPs, and are divided into twelve groups (EXPA-I-EXPA-XII). Of these, EXPA-XI members are specific to Medicago trunctula and alfalfa. Gene composition analysis revealed that the members of each individual subfamily shared a similar structure. Interestingly, about 56.3% of the cis-acting elements were predicted to be associated with abiotic stress, and the majority were MYB- and MYC-binding motifs, accounting for 33.9% and 36.0%, respectively. Our short-term treatment (≤24 h) with NaCl (200 mM) or PEG (polyethylene glycol, 15%) showed that the transcriptional levels of 12 MsEXPs in seedlings were significantly altered at the tested time point(s), indicating that MsEXPs are osmotic-responsive. These findings imply the potential functions of MsEXPs in alfalfa adaptation to high salinity and/or drought. Future studies on MsEXP expression profiles under long-term (>24 h) stress treatment would provide valuable information on their involvement in the response of alfalfa to abiotic stress.


Assuntos
Regulação da Expressão Gênica de Plantas , Genoma de Planta , Medicago sativa , Filogenia , Proteínas de Plantas , Estresse Fisiológico , Medicago sativa/genética , Medicago sativa/metabolismo , Medicago sativa/classificação , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismo , Estresse Fisiológico/genética , Família Multigênica , Perfilação da Expressão Gênica
5.
Mol Med ; 30(1): 64, 2024 May 17.
Artigo em Inglês | MEDLINE | ID: mdl-38760723

RESUMO

BACKGROUND: Insulin like growth factor II mRNA binding protein 3 (IGF2BP3) has been implicated in numerous inflammatory and cancerous conditions. However, its precise molecular mechanisms in endometriosis (EMs) remains unclear. The aim of this study is to examine the influence of IGF2BP3 on the occurrence and progression of EMs and to elucidate its underlying molecular mechanism. METHODS: Efects of IGF2BP3 on endometriosis were confrmed in vitro and in vivo. Based on bioinformatics analysis, RNA immunoprecipitation (RIP), RNA pull-down assays and Fluorescent in situ hybridization (FISH) were used to show the association between IGF2BP3 and UCA1. Single-cell spatial transcriptomics analysis shows the expression distribution of glutaminase 1 (GLS1) mRNA in EMs. Study the effect on glutamine metabolism after ectopic endometriotic stromal cells (eESCs) were transfected with Sh-IGF2BP3 and Sh-UCA1 lentivirus. RESULTS: Immunohistochemical staining have revealed that IGF2BP3 was upregulated in ectopic endometriotic lesions (EC) compared to normal endometrial tissues (EN). The proliferation and migration ability of eESCs were greatly reduced by downregulating IGF2BP3. Additionally, IGF2BP3 has been observed to interact with urothelial carcinoma associated 1 (UCA1), leading to increased stability of GLS1 mRNA and subsequently enhancing glutamine metabolism. Results also demonstrated that IGF2BP3 directly interacts with the 3' UTR region of GLS1 mRNA, influencing its expression and stability. Furthermore, UCA1 was able to bind with c-MYC protein, stabilizing c-MYC mRNA and consequently enhancing GLS1 expression through transcriptional promotion. CONCLUSION: These discoveries underscored the critical involvement of IGF2BP3 in the elevation and stability of GLS1 mRNA in the context of glutamine metabolism by interacting with UCA1 in EMs. The implications of our study extended to the identification of possible therapeutic targets for individuals with EMs.


Assuntos
Endometriose , Glutaminase , Glutamina , Estabilidade de RNA , RNA Longo não Codificante , Proteínas de Ligação a RNA , Feminino , Humanos , Glutaminase/metabolismo , Glutaminase/genética , RNA Longo não Codificante/genética , RNA Longo não Codificante/metabolismo , Endometriose/metabolismo , Endometriose/genética , Endometriose/patologia , Glutamina/metabolismo , Proteínas de Ligação a RNA/metabolismo , Proteínas de Ligação a RNA/genética , Proliferação de Células , Adulto , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Regulação da Expressão Gênica , Ligação Proteica
6.
Front Immunol ; 15: 1336311, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38585260

RESUMO

Envafolimab is a Chinese domestic innovative fusion of a humanized single-domain programmed death-ligand 1 (PD-L1) antibody (dAb) and human immunoglobulin IgG1 crystalline fragment (Fc) developed for subcutaneous injections. It was granted conditional market authorization by the China National Medical Product Administration (NMPA) in December 2021. Envafolimab is used to treat adult patients with previously treated microsatellite instability-high (MSI-H) or deficient mismatch repair (dMMR) advanced solid tumors, including patients with advanced colorectal cancer disease progression who were previously administered fluorouracil, oxaliplatin, and irinotecan, as well as other patients with advanced solid tumors who experienced disease progression after receiving standard treatment and had no other alternative treatment options. However, the lack of post-marketing clinical trial data requires conducting more clinical studies on the safety and efficacy of envafolimab in order to provide scientific basis and a reference for future therapeutic applications. In this paper, we report a case of severe skin necrosis and bleeding in the area of injection after subcutaneous administration of envafolimab in a patient diagnosed with hepatocellular carcinoma. We discuss issues that must be considered before administration of a PD-L1 inhibitor subcutaneously, which could induce immune mechanisms leading to skin necrosis in the area of injection.


Assuntos
Anticorpos Monoclonais Humanizados , Carcinoma Hepatocelular , Neoplasias Hepáticas , Adulto , Humanos , Imunoglobulina G , Progressão da Doença , Necrose
7.
Sci Rep ; 14(1): 8021, 2024 04 05.
Artigo em Inglês | MEDLINE | ID: mdl-38580710

RESUMO

The Phenome-Wide Association Study (PheWAS) is increasingly used to broadly screen for potential treatment effects, e.g., IL6R variant as a proxy for IL6R antagonists. This approach offers an opportunity to address the limited power in clinical trials to study differential treatment effects across patient subgroups. However, limited methods exist to efficiently test for differences across subgroups in the thousands of multiple comparisons generated as part of a PheWAS. In this study, we developed an approach that maximizes the power to test for heterogeneous genotype-phenotype associations and applied this approach to an IL6R PheWAS among individuals of African (AFR) and European (EUR) ancestries. We identified 29 traits with differences in IL6R variant-phenotype associations, including a lower risk of type 2 diabetes in AFR (OR 0.96) vs EUR (OR 1.0, p-value for heterogeneity = 8.5 × 10-3), and higher white blood cell count (p-value for heterogeneity = 8.5 × 10-131). These data suggest a more salutary effect of IL6R blockade for T2D among individuals of AFR vs EUR ancestry and provide data to inform ongoing clinical trials targeting IL6 for an expanding number of conditions. Moreover, the method to test for heterogeneity of associations can be applied broadly to other large-scale genotype-phenotype screens in diverse populations.


Assuntos
Diabetes Mellitus Tipo 2 , Humanos , Diabetes Mellitus Tipo 2/tratamento farmacológico , Diabetes Mellitus Tipo 2/genética , Estudos de Associação Genética , Fenótipo , Polimorfismo de Nucleotídeo Único , Receptores de Interleucina-6/genética
8.
Cardiovasc Diabetol ; 23(1): 123, 2024 Apr 05.
Artigo em Inglês | MEDLINE | ID: mdl-38581039

RESUMO

BACKGROUND: Diabetes is a predominant driver of coronary artery disease worldwide. This study aims to unravel the distinct characteristics of oral and gut microbiota in diabetic coronary heart disease (DCHD). Simultaneously, we aim to establish a causal link between the diabetes-driven oral-gut microbiota axis and increased susceptibility to diabetic myocardial ischemia-reperfusion injury (MIRI). METHODS: We comprehensively investigated the microbial landscape in the oral and gut microbiota in DCHD using a discovery cohort (n = 183) and a validation chohort (n = 68). Systematically obtained oral (tongue-coating) and fecal specimens were subjected to metagenomic sequencing and qPCR analysis, respectively, to holistically characterize the microbial consortia. Next, we induced diabetic MIRI by administering streptozotocin to C57BL/6 mice and subsequently investigated the potential mechanisms of the oral-gut microbiota axis through antibiotic pre-treatment followed by gavage with specific bacterial strains (Fusobacterium nucleatum or fecal microbiota from DCHD patients) to C57BL/6 mice. RESULTS: Specific microbial signatures such as oral Fusobacterium nucleatum and gut Lactobacillus, Eubacterium, and Roseburia faecis, were identified as potential microbial biomarkers in DCHD. We further validated that oral Fusobacterium nucleatum and gut Lactobacillus are increased in DCHD patients, with a positive correlation between the two. Experimental evidence revealed that in hyperglycemic mice, augmented Fusobacterium nucleatum levels in the oral cavity were accompanied by an imbalance in the oral-gut axis, characterized by an increased coexistence of Fusobacterium nucleatum and Lactobacillus, along with elevated cardiac miRNA-21 and a greater extent of myocardial damage indicated by TTC, HE, TUNEL staining, all of which contributed to exacerbated MIRI. CONCLUSION: Our findings not only uncover dysregulation of the oral-gut microbiota axis in diabetes patients but also highlight the pivotal intermediary role of the increased abundance of oral F. nucleatum and gut Lactobacillus in exacerbating MIRI. Targeting the oral-gut microbiota axis emerges as a potent strategy for preventing and treating DCHD. Oral-gut microbial transmission constitutes an intermediate mechanism by which diabetes influences myocardial injury, offering new insights into preventing acute events in diabetic patients with coronary heart disease.


Assuntos
Doença da Artéria Coronariana , Diabetes Mellitus , Microbioma Gastrointestinal , Humanos , Animais , Camundongos , Camundongos Endogâmicos C57BL , Fusobacterium nucleatum/fisiologia , Doença da Artéria Coronariana/etiologia
9.
Biochem Genet ; 2024 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-38557813

RESUMO

Cisplatin (DDP) is used for the clinical management of triple-negative breast cancer (TNBC). However, the development of drug resistance limits its therapeutic efficacy. Circular RNAs (circRNAs) are known to be involved in tumor DDP resistance. In our previous study, we reported that circ_0007823 expression is downregulated and correlated with adverse prognosis in TNBC. However, its association with DDP resistance remains unclear. This study aimed to determine the role of circ_0007823 and miR-182-5p in DDP-resistant TNBC and explore the underlying mechanisms. First, expression profiles circ_0007823, microRNA (miR)-182-5p, and forkhead box O1 (FOXO1) in TNBC cells were determined. Additionally, biological characteristics of cells, including apoptosis, cell cycle, proliferation, and migration, were analyzed using various assays. Luciferase reporter and rescue assays were used to determine the correlations among circ_0007823, miR-182-5p, and FOXO1 expression. MiR-182-5p was overexpressed in DDP-resistant TNBC cells. MiR-182-5p knockdown suppressed the invasiveness and increased the apoptosis of drug-resistant cells, contributing to G1 arrest and S phase reduction. Mechanistically, circ_0007823 targeted miR-182-5p, and its overexpression drastically reduced the promotional effects of the miR-182-5p mimic on the aggression and transfer ability of drug-resistant cells. Furthermore, FOXO1 overexpression increased the sensitivity of cells to DDP and reduced their malignant progression. Therefore, FOXO1 was established as the downstream target of miR-182-5p that may be used to treat DDP-resistant TNBC. In summary, circ_0007823 overexpression attenuated DDP resistance in TNBC via the miR-182-5p-FOXO1 axis, indicating the therapeutic potential of circ_0007823 DDP-resistant TNBC treatment.

10.
Front Plant Sci ; 15: 1333089, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38601301

RESUMO

Timely and accurate estimation of cotton seedling emergence rate is of great significance to cotton production. This study explored the feasibility of drone-based remote sensing in monitoring cotton seedling emergence. The visible and multispectral images of cotton seedlings with 2 - 4 leaves in 30 plots were synchronously obtained by drones. The acquired images included cotton seedlings, bare soil, mulching films, and PE drip tapes. After constructing 17 visible VIs and 14 multispectral VIs, three strategies were used to separate cotton seedlings from the images: (1) Otsu's thresholding was performed on each vegetation index (VI); (2) Key VIs were extracted based on results of (1), and the Otsu-intersection method and three machine learning methods were used to classify cotton seedlings, bare soil, mulching films, and PE drip tapes in the images; (3) Machine learning models were constructed using all VIs and validated. Finally, the models constructed based on two modeling strategies [Otsu-intersection (OI) and machine learning (Support Vector Machine (SVM), Random Forest (RF), and K-nearest neighbor (KNN)] showed a higher accuracy. Therefore, these models were selected to estimate cotton seedling emergence rate, and the estimates were compared with the manually measured emergence rate. The results showed that multispectral VIs, especially NDVI, RVI, SAVI, EVI2, OSAVI, and MCARI, had higher crop seedling extraction accuracy than visible VIs. After fusing all VIs or key VIs extracted based on Otsu's thresholding, the binary image purity was greatly improved. Among the fusion methods, the Key VIs-OI and All VIs-KNN methods yielded less noises and small errors, with a RMSE (root mean squared error) as low as 2.69% and a MAE (mean absolute error) as low as 2.15%. Therefore, fusing multiple VIs can increase crop image segmentation accuracy. This study provides a new method for rapidly monitoring crop seedling emergence rate in the field, which is of great significance for the development of modern agriculture.

11.
J Multidiscip Healthc ; 17: 1731-1742, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38659635

RESUMO

Purpose: This study aimed to examine the role of personal emotions and emotional contagion within organizations on the behavior and attitudes of healthcare personnel. This study is expected to provide a theoretical foundation for reducing resignation behaviors and improving healthcare quality. Materials and Methods: This study adopted a quantitative research method with a cross-sectional survey through an online questionnaire. The bootstrap method with 5000 iterations was used to validate the role of variables within a 95% confidence interval. SPSS 26.0 and Model 5 in Process 3.4 for SPSS were used for the data analysis. Results: This research involved 459 healthcare personnel, whose levels of role overload (3.821±0.925), emotional exhaustion (3.436±1.189), and turnover emotional contagion (3.110±1.099) were notably high. Role overload was positively related to turnover intention, with emotional exhaustion as a mediator. Notably, turnover emotional contagion exerted a positive moderating effect. Conclusion: This study emphasizes the adverse effects of emotional exhaustion and turnover emotional contagion in the Chinese context, offering practical recommendations for medical organizational managers to navigate turnover intention among healthcare personnel. This study suggests paying attention to the emotional state of healthcare personnel and providing adequate support resources. Managers should routinely assess and track turnover emotional contagion within the organization, fostering a positive emotional atmosphere.

12.
Diabetol Metab Syndr ; 16(1): 84, 2024 Apr 16.
Artigo em Inglês | MEDLINE | ID: mdl-38622732

RESUMO

BACKGROUND: Type 2 diabetes mellitus (T2DM), characterized by ß-cell dysfunction and insulin resistance (IR), presents considerable treatment challenges. Apelin is an adipocyte-derived factor that shows promise in improving IR; however, it is limited by poor targeting and a short half-life. In the present study, engineered small extracellular vesicles (sEVs) derived from Wharton's jelly-derived mesenchymal stem cells (WJ-MSCs) loaded with apelin were used to address the limitations of the therapeutic application of apelin. METHODS: WJ-MSCs were transduced to obtain engineered sEVs loaded with overexpressed apelin (apelin-MSC-sEVs) and the control sEVs (MSC-sEVs). T2DM mice were injected with apelin-MSC-sEVs and MSC-sEVs, and blood glucose monitoring, glucose and insulin tolerance tests, confocal microscopy, and immunocytochemical analysis were performed. IR models of 3T3-L1 adipocytes were employed to detect GLUT4 expression in each group using western blotting; the affected pathways were determined by measuring the changes in Akt and AMPK signaling and phosphorylation. RESULTS: Upon successful engineering, WJ-MSCs demonstrated significant overexpression of apelin. The genetic modification did not adversely impact the characteristics of sEVs, ranging from surface protein markers, morphology, to particle size, but generated apelin-overexpressed sEVs. Apelin-MSC-sEVs treatment resulted in notable enhancement of Akt and AMPK pathway activities within 3T3-L1 adipocytes and adipose tissues of T2DM mice. Furthermore, the apelin-loaded sEVs significantly reduced plasma glucose levels, increased pancreatic ß-cell proliferation, improved insulin and glucose tolerance, and modulated pro-inflammatory cytokine profiles, compared to mice treated with the control sEVs. CONCLUSION: Our study developed novel genetically engineered apelin-loaded sEVs derived from WJ-MSCs, and demonstrated their potent role in augmenting insulin sensitivity and regulating inflammatory responses, highlighting their therapeutic promise in T2DM management. The findings open new avenues for the development of clinically viable treatments for T2DM in humans using the apelin-loaded sEVs.

13.
J Ovarian Res ; 17(1): 82, 2024 Apr 16.
Artigo em Inglês | MEDLINE | ID: mdl-38627854

RESUMO

BACKGROUND: To establish a prognostic risk profile for ovarian cancer (OC) patients based on cancer-associated fibroblasts (CAFs) and gain a comprehensive understanding of their role in OC progression, prognosis, and therapeutic efficacy. METHODS: Data on OC single-cell RNA sequencing (scRNA-seq) and total RNA-seq were collected from the GEO and TCGA databases. Seurat R program was used to analyze scRNA-seq data and identify CAFs clusters corresponding to CAFs markers. Differential expression analysis was performed on the TCGA dataset to identify prognostic genes. A CAF-associated risk signature was designed using Lasso regression and combined with clinicopathological variables to develop a nomogram. Functional enrichment and the immune landscape were also analyzed. RESULTS: Five CAFs clusters were identified in OC using scRNA-seq data, and 2 were significantly associated with OC prognosis. Seven genes were selected to develop a CAF-based risk signature, primarily associated with 28 pathways. The signature was a key independent predictor of OC prognosis and relevant in predicting the results of immunotherapy interventions. A novel nomogram combining CAF-based risk and disease stage was developed to predict OC prognosis. CONCLUSION: The study highlights the importance of CAFs in OC progression and suggests potential for innovative treatment strategies. A CAF-based risk signature provides a highly accurate prediction of the prognosis of OC patients, and the developed nomogram shows promising results in predicting the OC prognosis.


Assuntos
Fibroblastos Associados a Câncer , Neoplasias Ovarianas , Humanos , Feminino , Prognóstico , Análise da Expressão Gênica de Célula Única , RNA-Seq , Neoplasias Ovarianas/genética , Microambiente Tumoral/genética
14.
Artigo em Inglês | MEDLINE | ID: mdl-38663834

RESUMO

Several noninvasive liver fibrosis tests have been developed and appear to predict the severity of fibrosis, possibly replacing invasive liver biopsy as a monitoring tool.1 The fibrosis-4 (FIB-4) score originally was proposed to help assess liver fibrosis in patients with human immunodeficiency virus and hepatitis C virus co-infection.1 FIB-4 has been used widely to monitor the severity of liver fibrosis, especially in patients with nonalcoholic fatty liver disease,2 now termed metabolic dysfunction-associated steatotic liver disease (MASLD).3.

15.
Front Bioeng Biotechnol ; 12: 1335377, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38456005

RESUMO

Mouth ulcers, a highly prevalent ailment affecting the oral mucosa, leading to pain and discomfort, significantly impacting the patient's daily life. The development of innovative approaches for oral ulcer treatment is of great importance. Moreover, a deeper and more comprehensive understanding of mouth ulcers will facilitate the development of innovative therapeutic strategies. The oral environment possesses distinct traits as it serves as the gateway to the digestive and respiratory systems. The permeability of various epithelial layers can influence drug absorption. Moreover, oral mucosal injuries exhibit distinct healing patterns compared to cutaneous lesions, influenced by various inherent and extrinsic factors. Furthermore, the moist and dynamic oral environment, influenced by saliva and daily physiological functions like chewing and speaking, presents additional challenges in local therapy. Also, suitable mucosal adhesion materials are crucial to alleviate pain and promote healing process. To this end, the review comprehensively examines the anatomical and structural aspects of the oral cavity, elucidates the healing mechanisms of oral ulcers, explores the factors contributing to scar-free healing in the oral mucosa, and investigates the application of mucosal adhesive materials as drug delivery systems. This endeavor seeks to offer novel insights and perspectives for the treatment of oral ulcers.

16.
FEBS J ; 2024 Mar 11.
Artigo em Inglês | MEDLINE | ID: mdl-38465368

RESUMO

LIM homeodomain transcription factor 1-alpha (LMX1a) is a neuronal lineage-specific transcription activator that plays an essential role during the development of midbrain dopaminergic (mDA) neurons. LMX1a induces the expression of multiple key genes, which ultimately determine the morphology, physiology, and functional identity of mDA neurons. This function of LMX1a is dependent on its homeobox domain. Here, we determined the structures of the LMX1a homeobox domain in complex with the promoter sequences of the Wnt family member 1 (WNT1) or paired like homeodomain 3 (Pitx3) gene, respectively. The complex structures revealed that the LMX1a homeobox domain employed its α3 helix and an N-terminal loop to achieve specific target recognition. The N-terminal loop (loop1) interacted with the minor groove of the double-stranded DNA (dsDNA), whereas the third α-helix (α3) was tightly packed into the major groove of the dsDNA. Structure-based mutations in the α3 helix of the homeobox domain significantly reduced the binding affinity of LMX1a to dsDNA. Moreover, we identified a nonsyndromic hearing loss (NSHL)-related mutation, R199, which yielded a more flexible loop and disturbed the recognition in the minor groove of dsDNA, consistent with the molecular dynamics (MD) simulations. Furthermore, overexpression of Lmx1a promoted the differentiation of SH-SY5Y cells and upregulated the transcription of WNT1 and PITX3 genes. Hence, our work provides a detailed elucidation of the specific recognition between the LMX1a homeobox domain and its specific dsDNA targets, which represents valuable information for future investigations of the functional pathways that are controlled by LMX1a during mDA neuron development.

17.
Acta Biomater ; 178: 68-82, 2024 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-38452962

RESUMO

Oral ulcers can significantly reduce the life quality of patients and even lead to malignant transformations. Local treatments using topical agents are often ineffective because of the wet and dynamic environment of the oral cavity. Current clinical treatments for oral ulcers, such as corticosteroids, have limitations and side effects for long-term usage. Here, we develop adhesive hydrogel patches (AHPs) that effectively promote the healing of oral ulcers in a rat model. The AHPs are comprised of the quaternary ammonium salt of chitosan, aldehyde-functionalized hyaluronic acid, and a tridentate complex of protocatechualdehyde and Fe3+ (PF). The AHPs exhibit tunable mechanical properties, self-healing ability, and wet adhesion on the oral mucosa. Through controlling the formula of the AHPs, PF released from the AHPs in a temporal manner. We further show that the AHPs have good biocompatibility and the capability to heal oral ulcers rapidly. Both in vitro and in vivo experiments indicate that the PF released from AHPs facilitated ulcer healing by suppressing inflammation, promoting macrophage polarization, enhancing cell proliferation, and inducing epithelial-mesenchymal transition involving inflammation, proliferation, and maturation stages. This study provides insights into the healing of oral ulcers and presents an effective therapeutic biomaterial for the treatment of oral ulcers. STATEMENT OF SIGNIFICANCE: By addressing the challenges associated with current clinical treatments for oral ulcers, the development of adhesive hydrogel patches (AHPs) presents an effective approach. These AHPs possess unique properties, such as tunable mechanical characteristics, self-healing ability, and strong adhesion to the mucosa. Through controlled release of protocatechualdehyde-Fe3+ complex, the AHPs facilitate the healing process by suppressing inflammation, promoting cell proliferation, and inducing epithelial-mesenchymal transition. The study not only provides valuable insights into the healing mechanisms of oral ulcers but also introduces a promising therapeutic biomaterial. This work holds significant scientific interest and demonstrates the potential to greatly improve the treatment outcomes and quality of life for individuals suffering from oral ulcers.


Assuntos
Benzaldeídos , Catecóis , Hidrogéis , Úlceras Orais , Humanos , Ratos , Animais , Hidrogéis/farmacologia , Adesivos , Qualidade de Vida , Materiais Biocompatíveis , Inflamação , Antibacterianos/farmacologia
18.
Chem Commun (Camb) ; 60(32): 4310-4313, 2024 Apr 16.
Artigo em Inglês | MEDLINE | ID: mdl-38533635

RESUMO

Benzaldehydes are indispensable building blocks in chemistry. However, the selective oxidation of toluene to benzaldehyde remains an ongoing challenge due to the low oxidation potential of benzaldehyde compared to toluene. We report herein a mild protocol that combines hydrogen atom transfer (HAT) with encapsulated air conditions and suitable catalyst loading for selective oxidation of toluene with high selectivity as well as good functional-group tolerance and a broad substrate scope for the synthesis of various high-value aromatic aldehydes. Moreover, the compatibility of this reaction with toluene derivatives of bioactive molecules further demonstrated the practicality of this approach. Mechanism studies have demonstrated that the collaboration between the oxygen quantity and the HAT catalytic system has a major impact on the high selectivity of the reaction. This study not only showcases the effectiveness of HAT strategies toward selective oxidation of toluene to benzaldehyde, but also provides an approach to controlling the selectivity of HAT reactions.

19.
ACS Appl Mater Interfaces ; 16(13): 15879-15892, 2024 Apr 03.
Artigo em Inglês | MEDLINE | ID: mdl-38529805

RESUMO

Tendon regeneration is greatly influenced by the oxidant and the inflammatory microenvironment. Persistent inflammation during the tendon repair can cause matrix degradation, tendon adhesion, and excessive accumulation of reactive oxygen species (ROS), while excessive ROS affect extracellular matrix remodeling and tendon integration. Herein, we used tannic acid (TA) to modify a decellularized tendon slice (DTS) to fabricate a functional scaffold (DTS-TA) with antioxidant and anti-inflammatory properties for tendon repair. The characterizations and cytocompatibility of the scaffolds were examined in vitro. The antioxidant and anti-inflammatory activities of the scaffold were evaluated in vitro and further studied in vivo using a subcutaneous implantation model. It was found that the modified DTS combined with TA via hydrogen bonds and covalent bonds, and the hydrophilicity, thermal stability, biodegradability, and mechanical characteristics of the scaffold were significantly improved. Afterward, the results demonstrated that DTS-TA could effectively reduce inflammation by increasing the M2/M1 macrophage ratio and interleukin-4 (IL-4) expression, decreasing the secretion of interleukin-6 (IL-6) and interleukin-1ß (IL-1ß), as well as scavenging excessive ROS in vitro and in vivo. In summary, DTS modified with TA provides a potential versatile scaffold for tendon regeneration.


Assuntos
Antioxidantes , Polifenóis , Alicerces Teciduais , Humanos , Alicerces Teciduais/química , Antioxidantes/farmacologia , Espécies Reativas de Oxigênio , Tendões , Anti-Inflamatórios/farmacologia , Inflamação/tratamento farmacológico , Regeneração
20.
Heliyon ; 10(6): e27743, 2024 Mar 30.
Artigo em Inglês | MEDLINE | ID: mdl-38509892

RESUMO

Terahertz time-domain spectroscopy (THz-TDS) has been widely used for food and drug identification. The classification information of a THz spectrum usually does not exist in the whole spectral band but exists only in one or several small intervals. Therefore, feature selection is indispensable in THz-based substance identification. However, most THz-based identification methods empirically intercept the low-frequency band of the THz absorption coefficients for analysis. In order to adaptively find out important intervals of the THz spectra, an interval-based sparse ensemble multi-class classifier (ISEMCC) for THz spectral data classification is proposed. In ISEMCC, the THz spectra are first divided into several small intervals through window sliding. Then the data of training samples in each interval are extracted to train some base classifiers. Finally, a final robust classifier is obtained through a nonnegative sparse combination of these trained base classifiers. With l1 -norm, two objective functions that based on Mean Square Error (MSE) and Cross Entropy (CE) are established. For these two objective functions, two iterative algorithms based on the Alternating Direction Method of Multipliers (ADMM) and Gradient Descent (GD) are built respectively. ISEMCC transforms the problem of interval feature selection and decision-level fusion into a nonnegative sparse optimization problem. The sparse constraint ensures only a few important spectral segments are selected. In order to verify the performance of the proposed algorithm, comparative experiments on identifying the origin of Bupleurum and the harvesting year of Tangerine peel are carried out. The base classifiers used by ISEMCC are Support Vector Machine (SVM) and Decision Tree (DT). The experimental results demonstrate that the proposed algorithm outperforms six typical classifiers, including Random Forest (RF), AdaBoost, RUSBoost, ExtraTree, and the two base classifiers, in terms of classification accuracy.

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