International Journal of Molecular Sciences最新文献

Papillary thyroid cancer (PTC) is the 8th most common cancer among women overall. Licorice contains over 300 active compounds, many of them with anti-cancer properties. Glycyrrhetinic acid (GA) is a major component of licorice. The aim of this study was to investigate the potential anti-proliferative effects of licorice and GA on PTC cell cultures. Licorice extract (LE) was produced from the root and tested on BCPAP and K1 cell lines, as well as GA and aldosterone. We used the MTT test to investigate the anti-proliferative activity, the wound healing test for the migratory activity, and finally, we analyzed cell cycle distribution, apoptosis, and oxidative stress after LE, GA, or aldosterone incubation. Both LE and GA reduced cell viability at 48 h and cell migration at 24 h in both PTC cultures. Aldosterone reduced cell migration only in K1 cells. LE and GA induced cell cycle arrest in the G0/G1 phase in the BCPAP cell line, while LE and aldosterone induced it in the K1 culture. GA but not LE increased the apoptosis rate in both cell lines, whereas LE but not GA increased oxidative stress in both cultures. This study presents the first evidence of the in vitro anti-proliferative and anti-migratory activity of LE and GA on PTC.

Suppressor of cytokine signaling 2 (SOCS2), an E3 ubiquitin ligase, regulates the JAK/STAT signaling pathway, essential for cytokine signaling and immune responses. Its dysregulation contributes to cardiovascular diseases (CVDs) by promoting abnormal cell growth, inflammation, and resistance to cell death. This study aimed to elucidate the molecular mechanisms underlying the interactions between Lumbricus-derived proteins and peptides and SOCS2, with a focus on identifying potential therapeutic candidates for CVDs. Utilizing a multifaceted approach, advanced computational methodologies, including 3D structure modeling, protein-protein docking, 100 ns molecular dynamics (MD) simulations, and MM/PBSA calculations, were employed to assess the binding affinities and functional implications of Lumbricus-derived proteins on SOCS2 activity. The findings revealed that certain proteins, such as Lumbricin, Chemoattractive glycoprotein ES20, and Lumbrokinase-7T1, exhibited similar activities to standard antagonists in modulating SOCS2 activity. Furthermore, MM/PBSA calculations were employed to assess the binding free energies of these proteins with SOCS2. Specifically, Lumbricin exhibited an average ΔG_binding of -59.25 kcal/mol, Chemoattractive glycoprotein ES20 showed -55.02 kcal/mol, and Lumbrokinase-7T1 displayed -69.28 kcal/mol. These values suggest strong binding affinities between these proteins and SOCS2, reinforcing their potential therapeutic efficacy in cardiovascular diseases. Further in vitro and animal studies are recommended to validate these findings and explore broader applications of Lumbricus-derived proteins.

Some studies suggest that low-grade inflammation and adipokines may be involved in mild cognitive impairment (MCI) and depression in subjects with type 2 diabetes; however, the available data concerning the elderly population are limited. Therefore, we conducted novel research to determine the serum adiponectin, hs-CRP and TNF-α levels in elderly diabetic patients with MCI and depressive symptoms and to identify the factors associated with MCI in this group. A total of 178 diabetic patients (mean age 84.4 ± 3.4 years) were screened for MCI and depressive symptoms. Various biochemical and biomarker data were collected. We found that patients with MCI and depressive symptoms demonstrated lower adiponectin levels and high hs-CRP and TNF-α. In this group, adiponectin concentration was negatively correlated with hs-CRP, TNF-α, HbA1c, and GDS-30 scores and positively correlated with MoCA scores. Multivariable analysis found the risk of MCI to be associated with higher TNF-α levels, fewer years of formal education, an increased number of comorbidities, and the presence of CVD. We concluded that low-grade inflammation and the presence of adipokines are associated with MCI and depressive symptoms in elderly diabetics. Further research should evaluate the suitability of Hs-CRP, TNF-α, and adiponectin as diagnostic markers for MCI and potential therapeutic targets.

Plasma-functionalized liquids (PFLs) are rich in chemical species, such as ozone, hydrogen peroxide, singlet oxygen, hydroxyl radical and nitrogen oxides, commonly referred to as reactive oxygen and nitrogen species (RONS). Therefore, manifold applications are being investigated for their use in medicine, agriculture, and the environment. Depending on the goal, a suitable plasma source concept for the generation of PFLs has to be determined because the plasma generation setup determines the composition of reactive species. This study investigates three PFL-generating plasma sources-two spark discharges and a flow dielectric barrier discharge (DBD) system-for their efficacy in eliminating microbial contaminants from tissue samples aiming to replace antibiotics in the rinsing process. The final goal is to use these tissues as a cell source for cell-based meat production in bioreactors and thereby completely avoid antibiotics. Initially, a physicochemical characterization was conducted to better understand the decontamination capabilities of PFLs and their potential impact on tissue viability. The results indicate that the flow DBD system demonstrated the highest antimicrobial efficacy due to its elevated reactive species output and the possibility of direct treatment of tissues while tissue integrity remained. Achieving a balance between effective large-scale decontamination and the biocompatibility of PFLs remains a critical challenge.

Dwarf bamboo (Fargesia denudata) is a crucial food source for the giant pandas. With its shallow root system and rapid growth, dwarf bamboo is highly sensitive to drought stress and nitrogen deposition, both major concerns of global climate change affecting plant growth and rhizosphere environments. However, few reports address the response mechanisms of the dwarf bamboo rhizosphere environment to these two factors. Therefore, this study investigated the effects of drought stress and nitrogen deposition on the physicochemical properties and microbial community composition of the arrow bamboo rhizosphere soil, using metagenomic sequencing to analyze functional genes involved in carbon and nitrogen cycles. Both drought stress and nitrogen deposition significantly altered the soil nutrient content, but their combination had no significant impact on these indicators. Nitrogen deposition increased the relative abundance of the microbial functional gene nrfA, while decreasing the abundances of nirK, nosZ, norB, and nifH. Drought stress inhibited the functional genes of key microbial enzymes involved in starch and sucrose metabolism, but promoted those involved in galactose metabolism, inositol phosphate metabolism, and hemicellulose degradation. NO₃^--N showed the highest correlation with N-cycling functional genes (p < 0.01). Total C and total N had the greatest impact on the relative abundance of key enzyme functional genes involved in carbon degradation. This research provides theoretical and technical references for the sustainable management and conservation of dwarf bamboo forests in giant panda habitats under global climate change.

The COVID-19 pandemic has overwhelmed healthcare systems and triggered global economic downturns. While vaccines have reduced the lethality rate of SARS-CoV-2 to 0.9% as of October 2024, the continuous evolution of variants remains a significant public health challenge. Next-generation medical therapies offer hope in addressing this threat, especially for immunocompromised individuals who experience prolonged infections and severe illnesses, contributing to viral evolution. These cases increase the risk of new variants emerging. This study explores miniACE2 decoys as a novel strategy to counteract SARS-CoV-2 variants. Using in silico design and molecular dynamics, blocking proteins (BPs) were developed with stronger binding affinity for the receptor-binding domain of multiple variants than naturally soluble human ACE2. The BPs were expressed in E. coli and tested in vitro, showing promising neutralizing effects. Notably, miniACE2 BP9 exhibited an average IC₅₀ of 4.9 µg/mL across several variants, including the Wuhan strain, Mu, Omicron BA.1, and BA.2 This low IC50 demonstrates the potent neutralizing ability of BP9, indicating its efficacy at low concentrations.Based on these findings, BP9 has emerged as a promising therapeutic candidate for combating SARS-CoV-2 and its evolving variants, thereby positioning it as a potential emergency biopharmaceutical.

A comprehensive genetic diversity analysis of 87 Passiflora germplasm accessions domesticated and cultivated for several years in the karst region of Guizhou, China, was conducted utilizing simple sequence repeat (SSR) fluorescent markers. These Passiflora species, renowned for their culinary and medicinal value, could bring significant economic and ecological benefits to the region. This study aimed to assess the genetic resources of these species and facilitate the selection of superior cultivars adapted to the karst environment. Our analysis revealed an abundance of SSR loci within the Passiflora transcriptome, with single-base repeats being the most prevalent type. Through rigorous primer screening and amplification, we successfully identified 27 SSR primer pairs exhibiting robust polymorphisms. Further interrogation at eight microsatellite loci revealed 68 alleles, underscoring the high level of genetic diversity present in the cultivated accessions. The average expected heterozygosity was 0.202, with the ssr18 locus exhibiting the highest value of 0.768, indicating significant genetic variation. The mean polymorphic information content (PIC) of 0.657 indicates the informativeness of these SSR markers. Comparative analyses of the cultivated and potential wild progenitors revealed distinct genetic variations among the different Passiflora types. Genetic structure and clustering analyses of the 87 accessions revealed seven distinct groups, suggesting gene flow and similarities among the resources. Notably, a DNA fingerprinting system was established using eight SSR primer pairs, effectively distinguishing the selected cultivars that had adapted to the karst mountainous region. This study not only deepens our understanding of Passiflora genetic resources in the karst environment but also provides a valuable reference for conservation, genetic improvement, and cultivar selection. The rich genetic diversity of the Passiflora germplasm underscores their potential for sustainable utilization in breeding programs aimed at enhancing the economic and ecological viability of these valuable plant species.

As cerium oxide nanoparticles (nCeO₂) continue to infiltrate aquatic environments, the resulting health risks to exposed aquatic organisms are becoming evident. Cytochrome P450 (CYP) enzymes are integral to the detoxification processes in these species. Herein, we conducted a genomic analysis of CYPs in Daphnia magna, encompassing phylogenetic relationships, gene structure, and chromosomal localization. We identified twenty-six CYPs in D. magna, categorizing them into four clans and seven families, distributed across six chromosomes and one unanchored scaffold. The encoded CYP proteins varied in length from 99 to 585 amino acids, with molecular weights ranging from 11.6 kDa to 66.4 kDa. A quantitative real-time PCR analysis demonstrated a significant upregulation of CYP4C1.4, CYP4C1.5, CYP4C1.6, CYP4c3.3, and CYP4c3.6 in D. magna exposed to 150 mg/L nCeO₂ for 24 h. The transcript levels of CYP4C1.3, CYP18a1, CYP4C1.1, and CYP4c3.9 were notably downregulated in D. magna exposed to 10 mg/L nCeO₂ for 48 h. A further transcriptomic analysis identified differential expression patterns of eight CYP genes, including CYP4C1.3, in response to nCeO₂ exposure. The differential regulation observed across most of the 26 CYPs highlights their potential role in xenobiotic detoxification in D. magna, thereby enhancing our understanding of CYP-mediated toxicological responses to metal nanoparticles in aquatic invertebrates.

This article explores the important, and yet often overlooked, solid-state structures of selected bioaromatic compounds commonly found in lignin hydrogenolysis oil, a renewable bio-oil that holds great promise to substitute fossil-based aromatic molecules in a wide range of chemical and material industrial applications. At first, single-crystal X-ray diffraction (SCXRD) was applied to the lignin model compounds, dihydroconiferyl alcohol, propyl guaiacol, and eugenol dimers, in order to elucidate the fundamental molecular interactions present in such small lignin-derived polyols. Then, considering the potential use of these lignin-derived molecules as building blocks for polymer applications, structural analysis was also performed for two chemically modified model compounds, i.e., the methylene-bridging propyl-guaiacol dimer and propyl guaiacol and eugenol glycidyl ethers, which can be used as precursors in phenolic and epoxy resins, respectively, thus providing additional information on how the molecular packing is altered following chemical modifications. In addition to the expected H-bonding interactions, other interactions such as π-π stacking and C-H∙∙∙π were observed. This resulted in unexpected trends in the tendencies towards the crystallization of lignin compounds. This was further explored with the aid of DSC analysis and CLP intermolecular energy calculations, where the relationship between the major interactions observed in all the SCXRD solid-state structures and their physico-chemical properties were evaluated alongside other non-crystallizable lignin model compounds. Beyond lignin model compounds, our findings could also provide important insights into the solid-state structure and the molecular organization of more complex lignin fragments, paving the way to the more efficient design of lignin-based materials with improved properties for industrial applications or improving downstream processing of lignin oils in biorefining processes, such as in enhancing the separation and isolation of specific bioaromatic compounds).

Cancer treatment continues to be a substantial problem due to tumor complexities and persistence, demanding novel therapeutic techniques. This review investigates the synergistic potential of combining photodynamic therapy (PDT) and tailored medication delivery technologies to increase mitochondrial toxicity and improve cancer outcomes. PDT induces selective cellular damage and death by activating photosensitizers (PS) with certain wavelengths of light. However, PDT's efficacy can be hampered by issues such as poor light penetration and a lack of selectivity. To overcome these challenges, targeted drug delivery systems have emerged as a promising technique for precisely delivering therapeutic medicines to tumor cells while avoiding off-target effects. We investigate how these technologies can improve mitochondrial targeting and damage, which is critical for causing cancer cell death. The combination method seeks to capitalize on the advantages of both modalities: selective PDT activation and specific targeted drug delivery. We review current preclinical and clinical evidence supporting the efficacy of this combination therapy, focusing on case studies and experimental models. This review also addresses issues such as safety, distribution efficiency, resistance mechanisms, and costs. The prospects of further research include advances in photodynamic agents and medication delivery technology, with a focus on personalized treatment. In conclusion, combining PDT with targeted drug delivery systems provides a promising frontier in cancer therapy, with the ability to overcome current treatment limits and open the way for more effective, personalized cancer treatments.