Materials Today Bio
·
2025
·
IF 10.2
Kai Liu,Jiangbo Shao,Beibei Han,Jianfeng Liu,Shuai Yan,Bin Liu,Yao Liu
Peripheral nerve regeneration (PNR) represents a substantial challenge in the medical field, primarily due to the limited regenerative capacity of the peripheral nerve system (PNS). Current research efforts are focused on developing advanced medical polymer materials to enhance nerve recovery. Despite significant progress, several critical issues remain unresolved, including biocompatibility, stability, mechanical strength, controlled degradation rates, and sustained release of therapeutic agents. This study examines the utilization of hyaluronic acid hydrogels, doped with mecobalamin (MeCbl) and conductive poly(3,4-ethylenedioxythiophene):polystyrene sulfonate (PEDOT:PSS), in combination with exogenous electrical stimulation (ES) for PNR of rats. The strategy utilizes the MeCbl hydrogel to create a regenerative microenvironment and provide nutritional support for nerve cells, while PEDOT:PSS facilitates enhanced electrical signal conduction. ES has been shown to promote PNR and functional recovery, thereby demonstrating considerable potential. This study aims to comprehensively analyze the synergistic effects and potential value of this combined therapeutic approach, providing novel insights and pathways for the effective PNR.
研究领域:
生物医学工程
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神经科学
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材料科学
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NUTRITION RESEARCH
·
2026
·
IF 3.6
Ningli Ye,Minghui Yu,Haixin Ju,Yuanyan Jiang,Yumeng Zhang,Lei Sun,Xiaohui Wu,Jing Chen,Hong Xu,Qian Shen
Imbalance of maternal diets can impair offspring development and contribute to congenital anomalies of the kidney and urinary tract (CAKUT). Excess maternal methionine intake is known to impair fetal development. The placenta serves as a crucial interface for maternal–fetal exchange and may contribute to these adverse outcomes. We hypothesize that excess methionine intake during pregnancy in mice increases the incidence of CAKUT in offspring. Therefore, we established a mouse model of 10% (w/w) methionine intake during pregnancy from Embryonic Day 8.5 to11.5 (E8.5-E11.5) and assessed the kidney phenotype. Crucial kidney developmental pathways were analyzed by RT–qPCR and immunofluorescence at E11.5. Changes in methionine metabolism in maternal plasma and placental tissues at E11.5 were analyzed using liquid chromatography–tandem mass spectrometry, and placental RNA–seq was performed. Offspring from dams exposed to excess methionine exhibited increased incidence of CAKUT (relative risk = 4.15, 95% confidence interval: 1.40-12.34, P = .010), primarily presenting as hydronephrosis and/or duplex collecting system. E11.5 embryonic kidneys showed shorter common nephric duct and decreased activity of the Gdnf/Ret/p-Akt pathway. At E11.5, homocysteine was elevated in the placentas, together with decreased mRNA expression of key metabolic enzymes betaine-homocysteine S-methyltransferase (Bhmt) and cystathionine γ-lyase (Cth) in the placentas. Concurrently, RNA-seq of E11.5 placentas revealed alterations in immune-inflammatory and vascular-related pathways. Overall, excessive maternal methionine intake in mice increased the incidence of CAKUT in offspring, which may be associated with altered activity of the Gdnf/Ret/PI3K/p-Akt pathway in embryonic kidneys as well as elevated placental homocysteine.
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INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES
·
2024
·
IF 7.7
Wencheng Zhao,Hengzheng Yang,Huizi Cui,Wannan Li,Shu Xing,Weiwei Han
Vitamin B 12 is a group of biologically active cobalamin compounds. In this study, we investigated the inhibitory effects of methylcobalamin (MeCbl) and hydroxocobalamin acetate (OHCbl Acetate) on protein tyrosine phosphatase 1B (PTP1B). MeCbl and OHCbl Acetate exhibited an IC 50 of approximately 58.390 ± 2.811 μM and 8.998 ± 0.587 μM, respectively. The K i values of MeCbl and OHCbl Acetate were 25.01 μM and 4.04 μM respectively. To elucidate the inhibition mechanism, we conducted a 500 ns Gaussian accelerated molecular dynamics (GaMD) simulation. Utilizing PCA and tICA, we constructed Markov state models (MSM) to examine secondary structure changes during motion. Our findings revealed that the α-helix at residues 37–42 remained the most stable in the PTP1B-OHCbl Acetate system. Furthermore, upon binding of OHCbl Acetate or MeCbl, the WPD loop of PTP1B moved inward to the active pocket, forming a closed conformation and potentially obstructs substrate entry. Protein-ligand interaction analysis and MM-PBSA showed that OHCbl Acetate exhibited lower binding free energy and engaged in more residue interactions with PTP1B. In summary, our study confirmed the substantial inhibitory activity of OHCbl Acetate against PTP1B, with its inhibitory potency notably surpassing that of MeCbl. We demonstrated potential molecular mechanisms of OHCbl Acetate inhibiting PTP1B.
研究领域:
生物化学
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药物化学
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计算生物学
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Frontiers in Bioscience-Landmark
·
2023
·Vol. 28
·期 11
·298
·
IF 3.1
Fengshi Zhang,Qicheng Li,Bo Ma,Meng Zhang,Yuhui Kou
Background: Severe peripheral nerve injuries, such as deficits over long distances or proximal nerve trunk injuries, pose complex reconstruction challenges that often result in unfavorable outcomes. An innovative approach to repairing severe peripheral nerve damage involves using conduit suturing for nerve transposition repair. Cylindrical nerve guides are typically unsuitable for nerve transposition repair. Moreover, postsurgical adjuvant treatment is essential to promote the development of axonal lateral sprouts, proximal growth, and the restoration of neurostructure and function. The purpose of this research is to assess the impact of chitosan-based conduits with varying inner diameters on nerve transposition repair when combined with modified formula Radix Hedysari (MFRH). Methods: Using chitosan, we created conduits with varying inner diameters on both ends. These conduits were then utilized to repair the distal common peroneal and tibial nerves in SD rats using the proximal common peroneal nerve. Subsequently, MFRH was employed as a supplementary treatment. The assessment of the repair’s effectiveness took place 16 weeks postsurgery, utilizing a range of techniques, including the neurological nerve function index, neuroelectrophysiological measurements, muscle wet weight, and examination of nerve and muscle histology. Results: The outcomes of our study showed that following 16 weeks of postoperative treatment, MFRH had a significant positive impact on the recovery of neuromotor and nerve conduction abilities. Moreover, there was a significant increase in the ratio of wet weight of muscles, cross-sectional area of muscle fibers, quantity and structure of regenerated myelinated nerve fibers, and the count of neurons. Conclusions: A combination of chitosan-based chitin conduits possessing different inner diameters and MFRH can considerably promote the regeneration and functional recovery of damaged nerves, which in turn enhances nerve transposition repair efficacy.
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