Cell Biochemistry and Biophysics最新文献

Chronic inflammation plays a pivotal role in the development and progression of cardiovascular diseases (CVDs), posing a significant threat to global health. This study presents the synthesis and comprehensive characterization of N-(2,3-dihydrobenzo[b][1,4]dioxin-6-yl)-6-nitrobenzo[d][1,3]dioxole-5-carboxamide (EMC), a promising therapeutic candidate for inflammation-related CVD treatment. Insights into EMC's physicochemical properties were gained through density functional theory (DFT) studies, revealing an energy gap, ΔE (E_HOMO-E_LUMO) = 2.97 eV. Hirshfeld surface analysis and molecular electrostatic potential (MEP) elucidated its crystal packing and charge distribution. Pharmacokinetic predictions (Swiss ADME and pkCSM) indicated EMC's drug-like behaviour, supporting its therapeutic potential. Molecular docking demonstrated selective COX-2 inhibition by EMC, with a docking score of -8.02 kcal/mol and key interactions involving ARG A:376, VAL A:538, ASN A:537, and GLN A:374. The results underscore the potential of EMC as a selective COX-2 inhibitor, offering anti-inflammatory benefits in CVD management. Furthermore, EMC exhibited promising antioxidant characteristics with IC₅₀ values of 21.56 ± 3.99 μM (ABTS) and 41.9 ± 5.17 μM (DPPH). This preliminary investigation contributes significantly to the development of novel therapeutic agent EMC for inflammation related CVDs, transiting for future in vitro and in vivo COX-2 inhibition studies.

In this study, a series of benzoxazole-linked pyrazole compounds (20a-t) were synthesized and tested for their antiproliferative activity. Their effects on lung cancer (A549) and normal lung (CCD-34Lu) cell lines were evaluated using the MTT assay. Among them, compounds 20m and o showed strong antiproliferative effects, with IC₅₀ values of 7.64 and 15.82 µM, respectively, and selectivity indices of 2.84 and 1.95 in favor of cancer cells. ELISA tests demonstrated that both compounds statistically significantly reduced VEGFR-2 protein levels by 24.8 and 28.7% at their respective IC₅₀ values, indicating potential antiangiogenic properties. Molecular docking studies supported these findings by showing favorable binding of 20m and o to the VEGFR-2 receptor, with binding energies of -7.33 kcal/mol and -7.22 kcal/mol, respectively. Overall, compounds 20m and o stand out as promising candidates for further development as anticancer drugs.

Curcumin is a polyphenol with medicinal properties, including antioxidant properties. It scavenges free radicals by increasing glutathione transferase activity. It is shown to inhibit the aggregation of proteins such as α-synuclein and amyloid β-peptide. In our study, BSA samples were incubated at 65 °C and then analyzed for aggregate formation. Furthermore, curcumin was examined for its anti-aggregatory potential. The inspection of aggregates was done using various spectrophotometric assays like UV-absorbance, congo red, turbidity, and CD spectra, as well as spectrofluorometric measurements such as intrinsic and ThT fluorescence. Visualisation of aggregates was done by transmission electron microscopy. BSA was incubated at 65 °C for 124 h. Intrinsic fluorescence and UV-absorbance showed increased spectra, suggesting unfolding of BSA. Aggregate formation was confirmed by increased ThT intensity, 15 nm red shift in CR absorbance, and appearance of a peak at 218 nm in CD spectra. Addition of 60 µM curcumin was found to be an effective concentration that inhibits the BSA aggregation as validated by decreased ThT fluorescence and CR absorbance. The UV-absorbance, intrinsic fluorescence, and reappearance of peaks at 208 and 222 nm in CD spectra confirmed that curcumin helps to maintain the native contacts of BSA and protects it from unfolding as well as aggregation. Protein aggregates are associated with various pathological conditions. In this study, curcumin was found to be a potential therapeutic molecule to clear aggregates in vitro. These results suggest developing a clinically used imitative of curcumin and related compounds.

Obesity is a condition where disproportionate body fat accumulation, leads to adverse health issues. Amaranthus tricolor is a popularly consumed leafy vegetable with reported therapeutic effects, including anti-inflammatory and hepatoprotective activities. Presently, the potential of terpenoids identified in the leaf extracts of A. tricolor was explored to manage obesity. Initially, the Total Terpenoid Content (TTC) and antioxidant potential of the hexane extract (HE) and methanolic extract (ME) was explored. Since, HE displayed better terpenoid content and antioxidant potential, its Gas Chromatography-Mass Spectrometry (GC-MS) chromatogram was used to identify and shortlist the terpenoids (1,2-15,16-Diepoxyhexadecane, α-tocopherol, Chondrillasterol, γ-tocopherol, Neophytadiene, Phytol and Squalene) present in it for in silico analysis. Network Pharmacology approach was utilised to identify hub genes (AKT1, HSP90AA1, PIK3CA, and SRC) of the shortlisted terpenoids. Molecular docking and simulation studies of the hub genes was performed using AutoDock Vina and GROMACS. α-tocopherol, Chondrillasterol and γ-tocopherol were shortlisted as the most promising terpenoids with potential to manage obesity by modulating the PI3K/AKT pathway. The current study highlighted the potential of terpenoids present in A.tricolor to alleviate obesity and provided strong theoretical indications to develop therapeutic interventions using such compounds.

Coronary heart disease (CHD) is a disease caused by organic and functional coronary artery stenosis, resulting in a reduced oxygen supply to the heart. This study aimed to investigate the mechanism via which Luteolin regulates the Sirt1/Nrf2 pathway to inhibit ferroptosis in human umbilical vein endothelial cells (HUVEC) associated with CHD. An ox-LDL-induced HUVEC cell model with Sirt1 silencing and Luteolin treatment was established. The silencing efficiency of Sirt1 was validated using quantitative reverse transcription polymerase chain reaction (qRT-PCR) and Western blot analysis. The results of molecular docking and DARTS experiments showed that Luteolin could effectively bind Sirt1. Subsequently, we measured the expression of Nrf2 and Sirt1, cell viability, MDA, GSH, Fe²⁺ levels, lipid ROS content, expression of ferroptosis-related proteins GPX4, FTH, FTL, and cell migration parameters. The results showed that Luteolin could activate the Sirt1/Nrf2 axis and effectively inhibit ox-LDL-induced ferroptosis in HUVEC. Experimental results revealed that Luteolin could enhance HUVEC cell viability, decrease MDA, Fe²⁺, and ROS levels, increase GSH levels, promote the expression of HO-1, GPX4, FTH, FTL, inhibit the expression of ACSL4 and TFRC, and enhance the migration capability of HUVEC cells. Moreover, silencing Sirt1 reversed the effects of Luteolin on the activation of Sirt1 and Nrf2, confirming the dependence of these effects on the Sirt1/Nrf2 signaling pathway. In conclusion, this study indicates that Luteolin could inhibit ferroptosis in HUVEC in CHD by modulating the Sirt1/Nrf2 axis, providing a basis for further research on strategies for preventing and treating CHD and related diseases.