Current Issues in Molecular Biology最新文献

While Ginsenoside Re has been shown to protect the central nervous system, reports of its effects on memory in the model of scopolamine-induced memory impairment are rare. The aim of this study was to investigate the effects of Ginsenoside Re on scopolamine (SCOP)-induced memory damage and the mechanism of action. Male ICR mice were treated with SCOP (3 mg/kg) for 7 days and with or without Ginsenoside Re for 14 days. As evidenced by behavioral studies (escape latency and cross platform position), brain tissue morphology, and oxidative stress indicators after Ginsenoside Re treatment, the memory damage caused by SCOP was significantly ameliorated. Further mechanism research indicated that Ginsenoside Re inhibited cell apoptosis by regulating the PI3K/Akt/Nrf2 pathway, thereby exerting a cognitive impairment improvement effect. This research suggests that Ginsenoside Re could protect against SCOP-induced memory defects possibly through inhibiting oxidative stress and cell apoptosis.

Inflammation is a tightly regulated process involving immune receptor recognition, immune cell migration, inflammatory mediator secretion, and pathogen elimination, all essential for combating infection and restoring damaged tissue. However, excessive inflammatory responses drive various human diseases. The autonomic nervous system (ANS) is known to regulate inflammatory responses; however, the detailed mechanisms underlying this regulation remain incompletely understood. Herein, we aimed to study the anti-inflammatory effects and mechanism of action of the ANS in RAW264.7 cells. Quantitative PCR and immunoblotting assays were used to assess lipopolysaccharide (LPS)-induced tumor necrosis factor α (TNFα) expression. The anti-inflammatory effects of catecholamines (adrenaline, noradrenaline, and dopamine) and acetylcholine were examined in LPS-treated cells to identify the receptors involved. Catecholamines inhibited LPS-induced TNFα expression by activating the β2 adrenergic receptor (β2-AR). β2-AR activation in turn downregulated the expression of Toll-like receptor 4 (TLR4) by stimulating protein kinase A (PKA) phosphorylation, resulting in the suppression of TNFα levels. Collectively, our findings reveal a novel mechanism underlying the inhibitory effect of catecholamines on LPS-induced inflammatory responses, whereby β2-AR activation and PKA phosphorylation downregulate TLR4 expression in macrophages. These findings could provide valuable insights for the treatment of inflammatory diseases and anti-inflammatory drug development.

Sugar beet hybrids are essential in modern agriculture due to their superior yields, disease resistance, and adaptability. This study investigates the role of the Rz2 gene in conferring resistance to beet necrotic yellow vein virus (BNYVV) in 14 sugar beet hybrids cultivated in Kazakhstan, including local and European varieties. The Rz2 gene, encoding a CC-NB-LRR protein, is a known resistance factor against BNYVV. Using RT-qPCR, we assessed Rz2 expression and detected BNYVV in bait plants inoculated with virus-infested soil. Our findings identified two highly resistant varieties: the Kazakh cultivar 'Abulhair' and the French line 22b5006. Additionally, the Kazakh cultivar 'Pamyati Abugalieva' and the French hybrid 'Bunker' exhibited increased resistance, suggesting involvement of other resistance loci. Notably, the Danish hybrid 'Alando', despite resistance to rhizomania, did not effectively resist BNYVV, highlighting possible evasion of its genetic factors by local virus strains. Our results emphasize the importance of Rz2 in resistance breeding programs and advocate for further research on additional resistance genes and the genetic variability of BNYVV in Kazakhstan. This work pioneers the molecular evaluation of BNYVV resistance in sugar beet in Kazakhstan, contributing to sustainable disease management and improved sugar beet production.

Due to continuous application as a flavoring agent in the pesticide, pharmaceutical, and food industries, methyl eugenol (ME) persists in the environment and causes deleterious impacts including cytotoxicity, genotoxicity, and liver damage. This study utilized a comprehensive approach, integrating toxicokinetics, metabolomics, and gut microbiota analysis, to explore the mechanisms behind ME-induced hepatotoxicity in mice. The study observed significant rises in ALT and AST levels, along with significant weight loss, indicating severe liver damage. Toxicokinetic data showed delayed Tmax and plasma accumulation after 28 days of repeated ME exposure at doses of 20 mg/kg, 40 mg/kg, and 60 mg/kg. The metabolomic analysis pinpointed four critical pathways-TCA cycle; alanine, aspartate, and glutamate metabolism; arginine biosynthesis; and tyrosine metabolism-linked to 20 potential biomarkers. Gut microbiota analysis revealed that extended ME exposure led to microbial imbalance, particularly altering the populations of Akkermansia, Prevotella, and Ruminococcus, which are key to amino acid metabolism and the TCA cycle, thus contributing to hepatotoxicity. However, the causal relationship between changes in gut microbiota and liver metabolite levels still requires further in-depth research. This study underscores the significant role of liver metabolites and gut microbiota in ME-induced liver damage.

In recent years, several studies have shown the antioxidant and antihypertensive potential of bioactive peptides. Thus, bioactive peptides are likely to be a valuable substance for the development of functional foods. There are a wide variety of sources of these peptides, including several cereals. Teff is an Ethiopian-rooted cereal with an interesting nutritional profile, mainly due to its high amount of protein. In this study, teff flour was subjected to a defatting process for optimizing the protein extraction. Such extraction was performed by precipitation from its isoelectric point, a crucial step that separates the protein from other components based on their charge. The protein obtained was subjected to enzymatic hydrolysis by pepsin and Cynara cardunculus L. The antihypertensive (angiotensin-I-converting enzyme -ACE-I- inhibitory activity) and antioxidant activity (2,2-diphenyl-1-picrylhydrazyl -DPPH- radical scavenging activity) of the peptides were determined. According to the IC₅₀ values, the results obtained showed that the peptides from teff flour show promising bioactivity compared to other cereals. Furthermore, the peptides from teff flour obtained from C. cardunculus L. showed higher antioxidant activity (defatted teff flour -DTF-: 0.59 ± 0.05; protein extract -EP- : 1.04 ± 0.11) than those obtained with pepsin (DTF: 0.87 ± 0.09; EP: 1.73 ± 0.11). However, C. cardunculus L. hydrolyzate peptides showed lower inhibitory activity of ACE-I (DTF: 0.59 ± 0.07; EP: 0.61 ± 0.05) than the pepsin hydrolyzate (DTF: 0.15 ± 0.02; EP: 0.33 ± 0.05).

This study explores the role of the von Hippel-Lindau (VHL) tumor suppressor gene and Lon protease in the development of clear cell renal carcinoma (ccRCC) through mechanisms involving inflammation and reactive oxygen species (ROS) accumulation in kidney cells. By examining the impact of VHL on the early stages of kidney cancer development, this research highlights the contributions of inflammation and ROS, as well as the involvement of Lon protease. The findings reveal increased Lon expression and ROS levels in VHL-knockdown HK-2 cells, along with elevated phospho-c-Jun N-terminal kinase (JNK) levels, emphasizing the complex interplay between VHL, Lon protease, inflammation, and ROS in kidney cell models. These insights point to potential therapeutic pathways for ccRCC.

Growing scientific evidence suggests a link between the expression of toll-like receptor 4 (TLR4) and cervical cancer carcinogenesis. Specifically, a close relation between TLR4 expression and FIGO stage, lymph node metastases, and tumor size has been reported in cervical cancer. In the present study, we aimed to evaluate the relationship between TLR4 expression levels and human papillomavirus (HPV) infection and/or high-risk (hr) HPV integration status in patients with a histological diagnosis of high-grade squamous intraepithelial lesion (H-SIL), and squamous cell carcinoma (SCC) of the uterine cervix. Sixty biopsies of cervical neoplasia, comprising H-SIL (n = 20) and SCC (n = 40), were evaluated for TLR4 expression by immunohistochemistry. All samples were positive for high-risk HPV as confirmed by in situ hybridization (ISH) and broad-spectrum PCR followed by Sanger sequencing analysis. The intensity of TLR4 staining was higher in tissues negative for intraepithelial lesion or malignancy (NILM) than in H-SIL, and further reduced in SCC. Moreover, statistically significant differences have been observed in the percentage of TLR4 expression between NILM and H-SIL and between H-SIL and SCC, with higher percentages of expression in H-SIL than in SCC. Our results showed a significant downregulation of TLR4 in HPV-related H-SIL and SCC, compared to NILM. These data support the hypothesis that TLR4 expression is suppressed in HPV-driven oncogenesis.

Galectin-3 (Gal-3) has been demonstrated to play a pivotal role in the pathogenesis of several fibrotic disorders. A number of studies have examined the relationship between galectin-3 levels and cardiac fibrosis in heart failure. Nevertheless, the role of galectin-3 in the etiology of supraventricular (SVa) and ventricular (Va) arrhythmias remains largely unexamined. The objective of this prospective study was to investigate the potential correlation between galectin concentration and the occurrence of idiopathic cardiac arrhythmias in pediatric patients. Biochemistry analysis was performed on 30 children (11-18 years; 14 boys and 16 girls). The control group consisted of 20 children. Cardiac arrhythmia was confirmed by a 24 h Holter ECG recording. Serum galectin-3 levels were measured via enzyme-linked immunosorbent assay (ELISA). Statistical analysis of the data showed significant associations between creatinine kinase (CK) and Gal-3 in patients with SVa (SVT-supraventricular tachycardia) arrhythmias, suggesting a potential effect of CK on Gal-3 levels. However, no correlation was identified between Gal-3 concentration and the occurrence of cardiac arrhythmias under investigation. We concluded that galectin-3 does not have the potential to be a biomarker in the diagnosis of idiopathic arrhythmias in pediatric patients.

TAFRO syndrome, first reported in 2010, is a systemic inflammatory disease with a rapid onset and potentially fatal course if not treated promptly and appropriately. The name is derived from the initial letters describing the characteristic symptoms of thrombocytopenia, anasarca, fever, reticulin fibrosis/renal failure, and organomegaly. It is sometimes considered a special subtype of idiopathic multicentric Castleman disease (iMCD) because lymph node biopsies often reveal the pathology findings seen in iMCD. However, its clinical manifestations and prognoses are not well documented. Since the clinical manifestations and prognoses of TAFRO syndrome differ significantly from those of iMCD, it is recognized as an independent disease concept and considered to partially overlap with the pathology of MCD. The pathogenesis of TAFRO syndrome remains largely unknown. Due to the lack of appropriate treatment, it often presents with multiple organ dysfunction and fatality. In this review, we summarized new findings on the pathogenesis of TAFRO syndrome and discussed current effective therapies and future treatment strategies.

The autophagy-lysosome axis is an evolutionarily conserved intracellular degradation pathway which constitutes an important component of host innate immunity against microbial infections. Here, we show that African swine fever virus (ASFV), one of most devastating pathogens to the worldwide swine industry, can reshape the autophagy-lysosome axis by recruiting the critical lysosome membrane proteins (LAMP1 and LAMP2) to viral factories while inhibiting autophagic induction in macrophages. The screening of viral membrane proteins led to the identification of several ASFV membrane proteins, exemplified by viral protein pEP153R, that could significantly alter the subcellular localization of LAMP1/2 when expressed alone in transfected cells. Further analysis showed that pEP153R was also a component of viral factories and could induce endoplasmic reticulum (ER) retention of LAMP1/2, leading to the inhibition of the fusion of autophagosomes with lysosomes. Interestingly, the ASFV mutant lacking EP153R could still actively recruit LAMP into viral factories (VFs) and inhibit autophagic flux, indicating the existence of a functional redundancy of other viral proteins in the absence of pEP153R and highlighting the complexity of ASFV replication biology. Taken together, our results reveal novel information about the interplay of ASFV with the autophagy-lysosome axis and a previously unrecognized function of ASFV protein pEP153R in regulating the cellular autophagic process.