Cell Biochemistry and Biophysics最新文献

Cancer is one of the prominent causes of death, and brain cancer accounts for about 2% of this figure, with glioma being the major type. This study aims to identify biomarker candidates for glioma subtypes, specifically glioblastoma (GBM) and oligodendroglioma (ODG), as well as to disclose repurposed drug candidates common to these brain tumors. Gene expression profiles were analyzed and integrated with data from proteomics interactions as well as miRNA regulation. 23 mutual core DEGs (differentially expressed genes) were identified. Correlation networks and protein interaction networks were constructed from these core DEGs. Hubs of the protein interaction networks (CALM1), miRNA - core DEG interaction network (SOX4, MTHFD2, and CALM1), and correlation networks such as ABCA2, TPPP, PPP1R16B, SPOCK3, and SPARC, as well as central miRNAs (hsa-miR-1-3p, hsa-miR-19b-3p, and hsa-miR-335-5p) were identified. Furthermore, candidate therapeutic agents were revealed. Docking-based virtual screening suggests that budesonide, sirolimus, cephaeline, etoposide, and staurosporine may target proteins upregulated in GBM and ODG, such as APOC, MTHFD2, and LPL, in addition to their actual targets. Particularly, sirolimus and protriptyline exhibited comparable binding affinities against MTHFD2 (-11.23 kcal/mol) and LPL (-7.45 kcal/mol), respectively, compared to their actual targets. The holistic network-based approach applied in this study may be advantageous in the illumination of these subtypes and may aid in the design of improved therapeutics in treatment of the studied gliomas.

The purpose of this research was to assess oxidative stress levels in colon cancer patients and examine their association with disease onset and progression. 176 individuals were recruited, comprising 106 colon cancer patients and 70 healthy controls. Serum oxidative stress marker levels of protein carbonyl (PCO), ischemia-modified albumin (IMA), malondialdehyde (MDA), and glutathione-S-transferase (GST) and antioxidant enzymes superoxide dismutase (SOD), glutathione peroxidase (GPX), and catalase (CAT) were quantified. The tumor markers carcinoembryonic antigen (CEA) and cancer antigen 19-9 (CA 19.9) were also evaluated. The levels of PCO, IMA, MDA, and GST were significantly increased (P < 0.01 for each) with a significant decrease in GPX and SOD levels (P < 0.01) when compared to the control group. No significant difference was noted in CAT levels. The tumor markers CEA and CA 19.9 were significantly increased in the patient group (P < 0.01). These results suggest an imbalance of oxidative/antioxidant status in favor of oxidative stress in patients with colon cancer. The study identifies oxidative stress as a major factor in the pathogenesis of colon cancer. Clinically, biomarkers such as IMA with more than 80% sensitivity can be powerful secondary aids to early detection or monitoring disease progression. The findings suggest that modulating oxidative stress would be therapeutic in the treatment of colon cancer.

Alzheimer's disease (AD) is a progressive neurodegenerative disorder characterized by cognitive decline, with limited therapeutic options and adverse effects associated with long-term pharmacological treatments. This study investigated the neuroprotective potential of Bryophyllum pinnatum (B. pinnatum) through integrative in silico and in vivo approaches. Network pharmacology and pathway enrichment analyses (KEGG, Cytoscape 3.10.1) were used to identify compound-target network association. Molecular docking using AutoDock Vina and molecular dynamics (MD) simulations for 200 ns using GROMACS were executed to assess the stability of the key ligands and targets. Cognitive impairment was induced in Wistar rats using scopolamine (1 mg/kg, i.p.). Animals were treated with B. pinnatum hydroalcoholic leaf extract (200 and 400 mg/kg, p.o.) and donepezil (3 mg/kg, i.p.) for 30 days. Cognitive and motor functions were evaluated via Morris water maze, elevated plus maze, locomotor activity, and grip strength tests. Biochemical assays measured acetylcholinesterase (ACHE) activity, β-amyloid (Aβ) levels, glutathione, and lipid peroxidation. Histopathological analysis of brain tissue assessed neuronal integrity. In silico analyses identified multiple phytoconstituents involved in AD-relevant pathways, including MAPK, PI3K-Akt, and cholinergic signaling. Diosmin exhibited high binding affinities to ACHE (-10.3 kcal/mol) and MAO-B (-11.2 kcal/mol), with stable binding confirmed via MD simulations. In vivo, B. pinnatum significantly improved cognitive performance, motor coordination, and antioxidant status while reducing Aβ aggregation and ACHE activity (p < 0.05). Histological findings showed reduced neuronal degeneration and neuroinflammation. These results highlight the multitarget neuroprotective potential of B. pinnatum, with diosmin emerging as a promising plant-derived candidate for AD therapeutics.

Chikungunya fever is an arboviral disease characterized by high fever, rash, and intense polyarthralgia, which may persist and evolve into a chronic condition, significantly impairing quality of life. The etiological agent, Chikungunya virus (CHIKV), is an alphavirus transmitted by Aedes aegypti mosquitoes and represents an increasing global public health concern due to its epidemic potential, economic burden, and the lack of specific antiviral therapies. In this context, in silico methodologies have become valuable tools in drug discovery and repurposing. This study aimed to predict natural compounds capable of inhibiting CHIKV non-structural protein 3 (nsP3). A total of 84,215 natural compounds from the ZINC20 database were screened through molecular docking using AutoDock Vina, with nsP3 as the target receptor. Ligand-protein interactions were visualized and analyzed with LigPlot+ and PyMOL. The top candidates were further refined through bioisosteric modifications using MolOpt, and their pharmacokinetic properties were predicted via the pkCSM platform. Among the optimized molecules, three bioisosteres, Chikv_bio1, Chikv_bio2, and Chikv_bio3, demonstrated favorable docking scores, interaction profiles, and ADMET properties, suggesting promising inhibitory activity against nsP3. These findings support the potential of natural compound-based drug design and highlight the importance of advancing to in vitro and in vivo validation to confirm the therapeutic relevance of these candidates and contribute to the development of specific treatments for Chikungunya fever.

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.