Biochemical and biophysical research communications最新文献

Parkinson's disease (PD) is a neurodegenerative disease primarily affecting the central nervous system and impacting both the motor system and non-motor systems. Although administration of L-DOPA is effective, it is not a fundamental treatment and has side effects such as diurnal fluctuation and dyskinesia, highlighting the need for new treatment methods. There is a growing interest in dopaminergic neuron transplantation as a potential treatment. Dopaminergic neurons derived from pluripotent stem (iPS) cells provide a valuable source for transplantation therapies. Developing an efficient method to differentiate iPS cells into dopaminergic cells is essential for cell transplantation therapy. While Cell differentiation is typically controlled by the addition of specific reagents, the physical characteristics of culture substrate, especially in the charge and stiffness, are also crucial factors in regulating differentiation. In this research, we show that two newly developed electrically charged polymeric hydrogels composed of cationic (C) and anionic (A) monomers inratio of 1-9 and 2 to 8 can significantly promote Dopaminergic neuron differentiation. Our findings emphasize the importance of culture substrates in effective dopaminergic cell differentiation.

Impaired fracture healing in diabetic patients leads to prolonged morbidity and increased healthcare costs. Methylglyoxal (MG), a reactive metabolite elevated in diabetes, is implicated in various complications, but its direct impact on bone healing remains unclear. Here, using a non-diabetic murine tibial fracture model, we demonstrate that MG directly impairs fracture healing. Micro-computed tomography revealed decreased volumetric bone mineral density in the callus, while callus volume remained unchanged, resulting in a brittle bone structure. This was accompanied by reduced expression of osteocalcin and bone sialoprotein, both critical for mineralization. Biomechanical analysis indicated that MG reduced the mechanical resilience of the fracture site without altering its elastic strength, suggesting that the impairment was not primarily due to the accumulation of advanced glycation end-products in the bone extracellular matrix. In vitro studies confirmed that non-cytotoxic concentrations of MG inhibited osteoblast maturation and mineralization. Transcriptomic analysis identified downregulation of Osterix, a key transcription factor for osteoblast maturation, without altering Runx2 levels, leading to decreased expression of key mineralization-related factors like osteocalcin. These findings align with clinical observations of reduced circulating osteocalcin levels in diabetic patients, suggesting that the detrimental effects of MG on osteoblasts may extend beyond bone metabolism. Our study highlights MG and MG-sensitive pathways as potential therapeutic targets for improving bone repair in individuals with diabetes and other conditions characterized by elevated MG levels.

The pink-colored Cypridina luciferase (CypLase∗) from Cypridina (Vargula) hilgendorfii contains an unknown chromophore (CypL∗), derived from Cypridina luciferin (CypL). When CypLase∗ was treated with NAD(P)H-FMN flavin reductase (FRase) and NADH, the luminescence intensity in the reaction mixture increased significantly after gentle tapping. This observation suggests that CypL∗ in CypLase is enzymatically converted to CypL by the reduced flavin (FMNH₂) through the FRase reaction, and the resulting complex of CypL and CypLase reacts with O₂ to emit light. Therefore, CypL∗ might be a dehydrogenated form of CypL and might serve as another storage form in Cypridina specimens.

Citrus canker poses a serious threat to a highly significant citrus fruit crop, this disease caused by one of the most destructive bacterial plant pathogens Xanthomonas citri pv. citri (Xcc). Bacterial plant diseases significantly reduce crop yields worldwide, making it more difficult to supply the growing food demand. The high levels of antibiotic resistance in Xcc strains are diminishing the efficacy of current control measures, necessitating the exploration of novel therapeutic targets to address the escalating antimicrobial resistance trend. Genome subtraction approach along with protein-protein network and coevolution analysis were used to identify potential drug targets in Xcc stain 306. The study involved retrieving the Xcc proteome from the UniProt database, eliminating paralogous proteins using CD-HIT (80 % identity cutoff), and selecting nonhomologous proteins through BLASTp (e-value <0.005). Essential proteins were identified using BLAST against the DEG (e-value cutoff 0.00001). 750 essential proteins were identified that are nonhomologous to citrus plant. Subsequent analyses included metabolic pathway assessment, subcellular localization prediction, and druggability analysis. Protein network analysis, coevolution analysis, protein active site identification was also performed. In conclusion, this study identified eight potential drug targets (GlmU, CheA, RmlD, GspE, FleQ, RpoN, Shk, SecB), highlighting RpoN, FleQ, and SecB as unprecedented targets for Xcc. These findings may contribute to the development of novel antimicrobial agents in the future that can efficiently control citrus canker disease.

Waterlogging stress is a significant abiotic factor that severely limits plant growth and development. Identifying genes involved in the waterlogging stress response and understanding the mechanisms by which plants resist waterlogging stress are therefore critical. In this study, we identified a specific role for two transcription factors, BPC1 and BPC2, in the waterlogging stress response of Arabidopsis thaliana. Waterlogging stress markedly upregulated the transcripts of BPC1 and BPC2 in Arabidopsis. Loss-of-function mutations in BPC1 and BPC2 decreased tolerance to waterlogging stress during the seedling growth stage. Physiological analyses demonstrated that the mutations of BPC1 and BPC2 aggravated waterlogging-induced increases in electrolyte leakage, malondialdehyde (MDA) content and hydrogen peroxide (H₂O₂) accumulation by modulating POD activity. Furthermore, quantitative real-time PCR (qRT-PCR) and dual-luciferase assays showed that BPC1 and BPC2 up-regulated the expression of peroxidase gene (Prx28). Collectively, our results indicate that BPC1 and BPC2 positively modulate Prx28 expression to affect the POD activity, modulating electrolyte leakage, MDA content and H₂O₂ accumulation under waterlogging stress. This study reveals the molecular mechanisms underlying waterlogging resistance in A. thaliana, providing new insights into this field.

Spectroscopic techniques and molecular docking were employed to explore the binding mechanism and structural characteristics of β-lactoglobulin (β-lg) with linoleic acid. The research revealed that the interaction between β-lg and linoleic acid was primarily governed by static quenching. The attachment of linoleic acid to β-lg happened naturally via hydrophobic forces. The interaction between β-lg and linoleic acid had minimal impact on the area surrounding the tryptophan and tyrosine residues in β-lg, and it does not notably change the secondary structure of β-lg. Results of molecular docking and molecular dynamics indicated that linoleic acid binds mainly to the hydrophobic cavity inside β-lg, closer to the tryptophan residues.At the same time the stability of the proteins in the complex was significantly improved compared to the free β-lg. The stability against oxidation and the shelf life of the β-lg/linoleic acid complex were evaluated as well. Compared to free linoleic acid, the complex exhibited lower peroxide and anisidine values, suggesting that its formation with β-lg reduced the creation of primary oxidation products.

Activin A, a gonadal protein, not only stimulates the pituitary to secrete follicle-stimulating hormone (FSH) but also plays a crucial role in regulating various cell behaviors, such as cell proliferation, differentiation, apoptosis, migration, and invasion. Studies have shown an association between activin A expression and tumor progression, highlighting its dual role in cancer. Similar to transforming growth factor-beta (TGF-β), activin A can have both pro-tumor and anti-tumor effects, for instance, it inhibits the migration of lung adenocarcinoma cells, while promotes the migration of triple-negative breast cancer cells. Therefore, activin A exerts context-dependent effects on different tumor cells. This review explores the biological functions of activin A in tumor progression and treatment, focusing on its influence on tumor cell proliferation, apoptosis, and metastasis. The aim is to offer insights and potential directions for future clinical cancer treatments.

Polycystic ovarian syndrome (PCOS) is a prevalent metabolic endocrine disorder in reproductive-aged women. This study aims to investigate the self-healing ability of PCOS and its potential impact on offspring. Methods: Female C57 BL/6J mice aged 4-5 weeks were administered letrozole (1 mg/kg/d) and a high-fat diet for 21 days to establish a PCOS model, and a control group was established. After modeling, the mice were divided into a PCOS model group and a self-healing group. After 14 days, the mice were mated, and the growth of their offspring was recorded. Subsequently, all mice were euthanized to collect serum, ovaries, and testes. The results showed that the self-healing group PCOS phenotype has shown improvement when compared to the model group. The findings from the offspring study indicate that all offspring in the model group died, while the self-healing group had offspring with a lower weight at 7 days and higher blood glucose levels. Additionally, the testicular morphology of male offspring in the self-healing group was poor. The conclusion drawn is that, after removing the pathogenic factors, the PCOS model group can self-heal. However, fertility remains impaired, which has an impact on their offspring.

Obesity and its related metabolic disorders seriously threaten our health and significantly reduce our life expectancy. The aim of the present study was to explore the effects of bone marrow mesenchymal stem cells (BMSCs) on high-fat diet (HFD)-induced obesity mice. The results demonstrated that BMSCs significantly reduced body weight, improved glucose tolerance and insulin sensitivity in obese mice. Further analysis showed that BMSCs could promote brown adipose tissue (BAT) activity and white adipose tissue (WAT) browning by increasing the expression of mitochondrial uncouple protein 1 (UCP1). Additionally, BMSCs markedly increase mitochondrial biogenesis, activate oxidative phosphorylation (OXPHOS) in adipose tissue, further contributing to energy metabolism regulation. Moreover, BMSCs were effective in inhibiting macrophage-related inflammation in adipose tissue, thereby mitigating obesity-associated inflammatory responses. Overall, our results lay the foundation for research on the potential of BMSCs as a promising strategy in alleviating obesity and related metabolic diseases.

Hepatic de novo lipogenesis (DNL) is increased by both carbohydrate intake and protein consumption. In hepatic fat synthesis, a key role is played by the induction of the hepatic expression of lipogenic genes, including Fasn, Scd1, and Srebf1. Regarding carbohydrate intake, increased blood glucose and insulin levels promote the expression of hepatic lipogenic genes. However, although amino acids serve as a carbon source for hepatic DNL during protein consumption, their effects on hepatic lipogenic gene expression remain unclear. We investigated the effects of amino acids on hepatic lipogenic gene induction using primary cultured mouse hepatocytes and hepatic Fasn reporter (l-FasnGLuc) mice. In primary cultured hepatocytes, lipogenic gene expression (Fasn, Scd1, Srebf1) was induced under postprandial-mimicking conditions (treatment with insulin and LXR agonist). When hepatocytes were stimulated with an amino acid mixture containing 20 amino acids, the induction of lipogenic gene expression was enhanced, but this effect disappeared when proline was removed from the mixture. Furthermore, when each amino acid was tested individually, only proline potentiated the induction of lipogenic gene expression in hepatocytes under postprandial-mimicking conditions. In mouse liver, continuous proline infusion via osmotic pump increased Fasn gene expression and showed a trend toward increased Srebf1 expression. In l-FasnGLuc mice, continuous proline infusion resulted in sustained enhancement of hepatic Fasn transcription, measured by secreted luciferase activity. These results demonstrate that proline enhances the induction of hepatic lipogenic gene expression both in vitro and in vivo.