Synchrotron radiation circular dichroism spectra of 2'-deoxyribonucleosides, as well as a few guanine nucleosides were recorded between 170-330 nm. The CD profile of each nucleoside is unique, and there is a general similarity in the SRCD patterns of deoxyribonucleosides and those recorded by a benchtop CD as previously reported. Furthermore, the locked nucleic acid derivative of guanine nucleoside (LNA-G) showed opposite CD profiles to the rest of the guanine nucleoside derivatives. The conformational parameters of the nucleosides were analyzed against the crystal structures available in the Cambridge Crystallographic Data Center. The pseudorotational phase angles of the guanine nucleoside derivatives in solution were also determined based on NMR coupling constants. Analyses showed no apparent correlation between pseudorotational phase angles and CD patterns.

The synthesis, characterization, double stranded (ds-DNA) and G-quadruplex DNA (G-DNA) binding affinities of a new Pt(II) complex of a new benzimidazole based ligand 6-(1-Imidazol-4-yl)-1,7-dihydroimidazo[4,5-f]benzimidazol-2-ol (idbo) is reported. The interactions of Pt(II) complex with ds-DNA and G-DNA have been studied by UV-Vis titration, UV thermal melting, fluorescent intercalator displacement (FID), competition dialysis and the findings were compared with the other known G-DNA binding compounds. The metal complex binds both G-DNA and ds-DNA according to UV titration results. Uv thermal melting studies show that the new Pt(II) complex stabilize G-quadruplex structure. A high G-DNA selectivity is calculated with FID results. Also, competition dialysis results prove the 1.6 selectivity on G-DNA binding of complex over ds-DNA.

Extracellular ATP (eATP) is a major component of the tumor microenvironment which has been shown to play an important role in inflammation and cancer. Previously, we have shown that eATP, through P2Y12 receptors, increased the levels of the pro-inflammatory enzyme cyclooxygenase 2 (COX-2) in tumor cells, which in turn imparted metastatic property to cancer cells. In a mouse model of lymphoma, we further showed that both the P2Y12 receptor-specific antagonist, AR-C 69931, and the P2Y6 receptor-specific antagonist, MRS 2578, significantly arrested tumor progression. In the case of tumor-bearing mice treated with AR-C 69931, a strong reduction in COX-2 expression was observed which in turn reduced metastasis. However, COX-2 expression was not altered in mice treated with MRS 2578. In this paper, we report that inhibition of the P2Y6 receptor acts through modulation of cell cycle proteins leading to cell cycle arrest. Our results show that blocking of P2Y6 receptors is a therapeutic alternative to arrest tumor growth and metastasis.

Oral lichen planus (OLP) is a chronic inflammatory condition that has been clinically linked with the risk of developing oral cancer. The present study aimed to determine the oxidative stress in oral lichen planus (OLP) by assessing the immunohistochemical (IHC) expression of 8-hydroxydeoxyguanosine (8-OHdG) in OLP tissue samples and comparing it with that of normal oral mucosa. The study group consisted of 30 formalin-fixed, paraffin-embedded (FFPE) tissue blocks from oral lichen planus (OLP) cases, while 10 normal oral mucosa samples served as the control group. Tissue sections of 5-micron thickness were prepared and immunostained with the 8-hydroxydeoxyguanosine (8-OHdG) antibody. The stained slides were examined under a light microscope, and statistical analysis was conducted using Fisher's exact test. A significant increase in oxidative DNA damage marker 8-OHdG expression ( < 0.05) was observed within the basal and suprabasal epithelial layers of lichen planus tissue samples. In contrast, no immunoreactivity was detected in the normal oral mucosa. Excessive production of reactive oxygen species (ROS) during chronic inflammation is believed to play a crucial role in inducing DNA damage. The mutagenic marker 8-hydroxydeoxyguanosine (8-OHdG) in oral lichen planus tissue highlights its potential as a biomarker for assessing the risk of inflammation-driven carcinogenesis. Further research, incorporating various oxidative stress markers and clinicopathological correlations, is essential to enhance early prediction of malignant transformation in oral lichen planus.

Osteoarthritis (OA) is a prevalent degenerative joint disease with limited diagnostic and therapeutic options. Recent studies suggest that nucleotide metabolism (NM) plays a key role in OA progression. This study aimed to identify NM-related genes involved in OA and explore their potential mechanisms. Transcriptomic data from the GEO database were analyzed using differential expression and machine learning approaches. Two key genes, AMPD3 and TYMS, were identified and validated through ROC analysis and clinical tissue samples. A nomogram based on these genes demonstrated strong diagnostic performance. Enrichment analysis revealed their involvement in multiple pathways, including oxidative phosphorylation. Immune infiltration analysis indicated correlations with immune cells. Drug prediction identified several candidate compounds; molecular docking further confirmed strong binding affinities-AMPD3 with AM095, and TYMS with deoxyuridine monophosphate. These findings suggest that AMPD3 and TYMS are key regulators in OA-related NM and may serve as novel biomarkers and therapeutic targets.

Hepatocellular carcinoma (HCC), which predominantly manifests as a malignant form of primary liver cancer, remains resistant to existing therapies in many patients. Therefore, elucidating the cellular processes and signaling networks driving HCC progression and discovering novel treatment targets remain key areas of research. , , and are closely associated with liver cancer, but the relationship between them is unclear. , , and levels were quantified using RT-qPCR. expression was analyzed through Western blotting. Liver tumor cell viability was assessed using CCK8 assays. The metastatic potential of cells was primarily evaluated using wound healing and Transwell assays. 's impact on tumors was validated through live animal experiments by inducing subcutaneous tumor formation in nude mice. RNAhybrid and TargetScan analyzed potential target regions in and . Our study demonstrates that reducing expression can inhibit hepatoma cell proliferation, migration, and invasive abilities. Specifically, knocking down can reduce the expression of . Knocking down can suppress liver cancer development in live animal models. In addition, can bind and and down-regulate the expression of . In summary, promotes the proliferation, migration, and invasion of HCC cells by inhibiting / axis.

The role of oleuropein (OLE) in K562 leukemia progression was investigated by evaluating its antiproliferative effect the XTT assay, oxidative damage through 8-OHdG and TAS/TOS measurements, and apoptotic activity using Caspase-3 assays. Total RNA was isolated from control and treated cells, followed by cDNA synthesis and RT-PCR analysis to assess mRNA expression of DNA repair-related genes. OLE reduced K562 leukemia cell viability in a time- and dose-dependent manner, with an IC of 244 µM at 72 h. Treatment with OLE decreased both total oxidant and antioxidant status, while increasing the oxidative stress index. However, changes in 8-OHdG and Caspase-3 levels were not statistically significant. Additionally, no significant differences were observed in the expression of XRCC1, APE1, NEIL1, and PARP1 genes after 72 h of treatment with 244 µM OLE. These findings suggest that OLE may possess anticancer potential and could contribute to the development of therapeutic strategies for hematological malignancies such as leukemia.

The stability of CRISPR-Cas9 endonuclease activity is essential for its effectiveness in molecular diagnostics and gene editing. Target sequences of Human Papillomavirus (HPV) types 16 and 18 were selected by generating a consensus sequence following multiple sequence alignment, to ensure high specificity. The single guide RNAs (sgRNAs) were designed by identifying Protospacer Adjacent Motif (PAM) sequences within the E6 gene of HPV-16 and HPV-18. High-fidelity DNA oligonucleotides were synthesized from Integrated DNA Technologies (IDT) and transcribed into single guide RNAs (sgRNAs). These sgRNAs were then assembled with Cas9 protein to form CRISPR-Cas9 ribonucleoprotein (RNP) complexes, which were subsequently lyophilized to enhance storage stability. Functional validation of the RNP complexes was performed over a period of up to 18 months using polymerase chain reaction (PCR), agarose gel electrophoresis (AGE), and SYBR Green-based real-time PCR (RT-PCR) to confirm endonuclease activity and cleavage efficiency. This study assessed the activity of lyophilized HPV-16 and HPV-18 CRISPR-Cas9-RNPs stored at 4 °C for up to 18 months. Results demonstrated that the ribonucleoprotein (RNP) complex consisting sgRNA retained significant endonuclease activity, supporting lyophilization as a viable strategy for enhancing the stability and shelf life of CRISPR-Cas9 complexes for long-term applications.

A series of conjugates of diterpenoid isosteviol (16-oxo--beyran-19-oic acid) and uracil (nucleoterpenoids) was synthesized and examined for their cytotoxicity against 9 human cancer cell lines. Nucleoterpenoids ,, exhibited the best cytotoxic activity against cancer cell lines M-HeLa, MCF-7, and PC3 (IC = 12.7-21.3 µM) among the synthesized compounds. The mechanisms of the cytotoxic effect of nucleoterpenoids and against M-HeLa cancer cell line (cervical carcinoma) were studied using flow cytofluorometry and enzyme-linked immunosorbent assay (ELISA). The results obtained indicated that and by acting on M-HeLa cancer cells reduced the mitochondrial membrane potential, caused oxidative stress, blocked anti-apoptotic protein Bcl-2, activated apoptosis-initiating caspase-9, thus inducing apoptosis occurring along the mitochondrial pathway. It should be emphasized that although isosteviol and uracil do not have cytotoxicity against human cancer cells, nucleoterpenoids ,, and containing isosteviol and uracil as fragments exhibited good cytotoxicity against M-HeLa, MCF-7, and PC3 cancer cells. Thus, it can be considered that conjugation of diterpenoid isosteviol and nucleic bases is a promising way to search for new cytotoxic agents of unusual structure.

The sodium salts of 2-formyl-1-cycloalkanones and α-(hydroxymethylene)alkanones, when reacted with cyanothioacetamide, produced equivalent cycloalkane ring fused pyridine-2(1)-thiones and substituted pyridone-2(1)-thiones. The corresponding pyridine S-glycosides were obtained in good yields from the later compounds by a successful coupling reaction with protected bromoarabinose or bromoxylose in KOH-acetone at room temperature and/or HDMS/(NH)SO. After ten minutes of room temperature reaction between the later compounds and NH-MeOH, excellent yields of the deprotected derivatives were produced. Using spectral data and fundamental analyses, the structure of the newly synthesized compounds were proved (IR, H NMR, and C NMR). All prepared thioglycoside substances had their antibacterial properties assessed and screened. Some thioglycoside derivatives turned out to be potent antibacterial agents.

Hepatitis C Virus (HCV) is highly a mutable RNA virus, primarily due to lack of proofreading activity in RNA-dependent RNA polymerase. This intrinsic feature leads to the generation of substantial intra-host variation, resulting in the formation of viral quasispecies. The 5' untranslated region (5'UTR) of the HCV genome is highly conserved across different genotypes and serves as a widely adopted target for genotyping in clinical practice. In this study, the performance of targeted short-read next-generation sequencing of the HCV 5' UTR using Ion Torrent technology was evaluated, with the dual aim of assigning genotypes and detecting low-frequency intra-host variants. The 5'UTR-based nested RT-PCR products were amplified for five clinical plasma samples and sequenced on the Ion Gene Studio S5 platform. The resulting reads were assembled to generate consensus sequences and subjected to comprehensive analysis for iSNVs, SNPs, and indels. Sequencing of the amplicons yielded short-read sequences of 200-300 nucleotides. Phylogenetic analyses using MEGA and Interactive Tree of Life demonstrated that all isolates clustered within genotype 3, with sub-clustering indicative of subtype 3a and other intra-genotypic variants. Fourteen SNPs and several low-frequency iSNVs most notably at positions 72, 78, and 128, with variant frequencies reaching up to ˜25% were detected. These findings underscore the method's ability to discriminate both genotype and sub-variant structure. Overall, this strategy enhances molecular epidemiology, investigations, enables robust transmission tracking, and supports individualized therapeutic decision-making, particularly in resource-limited diagnostic settings.

-methyladenosine (m6A) is the most plentiful internal modification event in eukaryotic RNAs and regulated dynamically by a variety of its cognate functional partners in a context-dependent manner, namely writers, erasers and readers. The YTHDF1 is a well-documented cytoplasmic m6A reader that can specifically recognize and interact with m6A its YT521-B homology (YTH) domain. In this study, the three methyl hydrogens of m6A mononucleotide were systematically swapped with four halogens (X = F, Cl, Br and I), totally resulting in the 4 single-, 10 double- and 20 triple-halogen modified counterparts of m6A (-halomethyladenosine, Xm6A). Energetic analyses and affinity assays indicated a moderate binding potency of m6A mononucleotide to YTHDF1 YTH domain, which can be improved by different single-halogen modifications. The electron-correlation calculations revealed that the affinity improvement is primarily donated from formation of additional halogen-π interactions with YTH aromatic cage upon the halogenations. Bromine, but not the bulky iodine, modification reaches the affinity maximum at Brm6A - this can be considered as a compromise between the favorable halogen-π interactions and the unfavorable steric effects caused by halogen modifications. For the same reason, single- and double-modifications generally contribute more favorably to YTH-Xm6A binding than triple-modifications. Further competition assays observed that the m6A mononucleotide and its single-modified Brm6A counterpart can competitively displace a m6A-containing RNA bound in the binding site of YTHDF1 YTH domain in moderate and high potencies, respectively, implying that halogen-modified Xm6A mononucleotides could be exploited as therapeutic strategy by competitively disrupting the cognate intermolecular interaction between YTH domain and RNA m6A.

Glioma represents the prevalent neoplasm type, distinguished by invasive growth and a significant rate of recurrence. This research investigates the prognostic significance and possible molecular mechanisms of miR-551a in gliomas, thereby offering a novel biomarker for gliomas treatment. This study selected 77 glioma patients and 52 craniocerebral injury patients from 2017 to 2023. The expression of miR-551a was assessed by qPCR. The ROC, Cox regression, and KM curve analyses were conducted to evaluate the diagnostic utility and prognostic value of miR-551a. The effects of inhibiting miR-551a on glioma cell functions were evaluated through CCK-8 and transwell assays. miR-551a target genes was conducted by GO and KEGG enrichment analyses, as well as PPI analysis, to elucidate potential gene regulatory relationship. miR-551a exhibited a significant up-regulation in the cerebrospinal fluid of glioma patients (P < 0.001). miR-551a possessed a robust predictive capacity for gliomas (AUC = 0.792, P < 0.001) and serves as a risk factor for unfavorable prognoses (HR = 3.858, P < 0.01), with patients exhibiting low levels of miR-551a showing favorable prognosis (P = 0.004). The inhibition of miR-551a diminished the proliferative (P < 0.05), migratory (P < 0.01), and invasive (P < 0.001) capabilities of glioma cells. miR-551a functioned as an oncogene, with CALM3 identified as critical regulatory targets (P < 0.001). miR-551a is a biological indicator for glioma prediction. It participates in the disease progression of glioma by regulating the functions of glioma cells via CALM3.

Four mixed ligand metal complexes have been synthesized from -phenylenediamine (OPD) Schiff base and a dicarboxylic acid (succinic acid). Using spectral examinations in the UV-Vis, FT-IR, mass, electron paramagnetic resonance, and nuclear magnetic resonance, the prepared ligand and the complexes have been characterized. Numerous methodologies have been employed to examine pharmacological activities, including those related to anti-oxidant, anti-microbial, and DNA binding. Utilizing the B3LYP/6-31G (d) basis set and the Gaussian-09 program, the Density Functional theory investigations have optimized the ligand and its metal complexes' molecular structures in order to investigate the theoretical properties. Furthermore, all complexes involving the interacting amino acids of the bacterial kinase (PDB ID: 7VKB) and fungal kinase (PDB ID: 6U6A) underwent molecular docking studies. In the results, metal complex [CuL(L)] showed good DNA binding ability, antimicrobial (Lowest MIC 1.3 µg/mL), antifungal (Lowest MIC 1.2 µg/mL) and anioxidant (Lowest IC 2.0 µg/mL) activities which ensure the good drug candidacy potentials of [CuL(L)].

Heart failure (HF) is not a disease but a combination of signs and symptoms caused by the failure of the heart to pump blood to support the circulatory system at rest or during activity. HF is the potential end stage of all heart diseases in which cardiomyopathies are a diverse group of cardiac disorders with distinct phenotypes, depending on the protein and pathways affected. Cardiomyopathies represent major causes of morbidity and mortality at all ages in humans in which hypertrophic cardiomyopathy (HCM) and dilated cardiomyopathy (DCM), are the most common. Among the different common diagnostic tests for heart failure such as physical examination, blood tests, chest X-rays, electrocardiogram (ECG), etc. ultrasound has also been used not only for diagnosis such as echocardiography but also for therapeutic purposes. The development of therapeutic strategies for HF aiming to improve the heart's function, delay progression of HF, and treat HF symptoms as well as to stimulate the capacity to regenerate cardiomyocytes stem cell therapy have been under intensive research interest. This narrative review aims to present the current understanding of the pathogenesis, diagnosis, and treatment of HF. Furthermore, as a perspective, this review navigates emerging therapies for HF by emphasizing on the use of low-intensity pulsed ultrasound (LIPUS) as a noninvasive therapy for (1) stimulation of the myocardial tissue reconstruction mechanisms; and (2) exploration of the molecular mechanisms behind the mechanotransduction from the muscle LIM protein (MLP), which is believed to be involved in human HF, using its expression vector glycosylphosphatidylinositol, GPI, anchor.

Live-cell imaging of intracellular proteins enables real-time observation of protein dynamics under near-physiological conditions, providing pivotal insights for both fundamental life science research and medical applications. However, due to limitations such as poor probe permeability and cytotoxicity associated with conventional antibody-based or genetically encoded labeling techniques, live-cell imaging remains a significant challenging. To address these limitations, here in this study, we developed and rigorously validated a novel aptamer-based fluorescent probe for real-time imaging of NEK9 kinase in living cells. First, through capture-SELEX, a DNA aptamer termed as Apt-011 which could selectively bind NEK9 was identified. Further, capitalizing on the small size, low immunogenicity, and synthetic flexibility of aptamers, we engineered a "signal-on" NEK9-specific aptamer-based fluorescent probe platform. This design leverages the aptamer's target--induced conformational change to physically separate the fluorophore-quencher pair, and it has been validated that this fluorescent probe platform could successfully visualize intracellular NEK9 in live-cells without obvious cytotoxicity (cell viability > 95% at working concentrations), offering new opportunities to study NEK9-associated signaling pathways. This work not only provides a robust tool for kinase research but also establishes a generalizable strategy to overcome key bottlenecks in live-cell imaging through rational aptamer engineering.

Colon cancer is a leading global malignancy with significant health burden. As key regulators of tumorigenesis, microRNAs (miRNAs) are implicated in colon cancer progression, yet the role of miR-1303-its clinical significance and molecular mechanism-remains unclear. This study aimed to investigate the regulatory effects of miR-1303 and validate its potential as an independent prognostic indicator. miR-1303 expression was analyzed qRT-PCR in 117 paired CRC tissues and adjacent normal tissues. Clinical relevance was evaluated Kaplan-Meier survival curves and Cox proportional hazards modeling. Functional assays (CCK-8, Transwell migration/invasion, luciferase reporter) were performed in SW480 and HCT116 cells. Target genes were predicted using miRDB and TargetScan. Rescue experiments confirmed miR-1303 regulates CRC progression by targeting TMEM108. miR-1303 was significantly upregulated in colon cancer tissues compared to normal tissues ( < 0.001) and correlated with advanced TNM stage ( = 0.021), lymph node metastasis ( = 0.005), poor differentiation ( = 0.031), and larger tumor size ( = 0.044). High miR-1303 expression predicted poorer overall survival ( = 0.001) and was recognized as an independent predictor of prognosis (HR = 2.096, 95% CI = 1.080-4.071). Functional studies revealed that miR-1303 inhibition suppressed colon cancer cell proliferation, migration, and invasion. Mechanistically, miR-1303 directly targeted the TMEM108, leading to its post-transcriptional repression. Upregulated miR-1303 in colon cancer served as a poor prognosis predictor. miR-1303 promotes tumor progression in colon cancer by targeting TMEM108.

Triple-negative breast cancer (TNBC) is an aggressive subtype characterized by a poor prognosis. MicroRNAs (miRNAs) play a crucial regulatory role in tumorigenesis, but the specific function and mechanism of miR-1266-5p in TNBC remain unclear.

This review comprehensively examines nitrogen heterocyclic thioglycosides as promising therapeutic candidates for the development of antiviral drugs. Our aim is to explore recent advancements and the therapeutic potential of their analogues. By integrating knowledge from diverse fields, we seek to understand how these compounds can be leveraged to create effective and targeted antiviral therapies. Our findings underscore the significant potential of nitrogen heterocyclic thioglycosides as viable options for future antiviral drug development, emphasizing their ability to specifically engage and modulate key pathways. This study concludes by highlighting the crucial role of these compounds in medicinal chemistry and their promise in contributing to the creation of novel and potent antiviral agents.

Monocytes, upon activation, are known to produce substantial levels of cytokines and increased expression of MHC-I. The status of zinc and the nature of the stimulating agent significantly influence the release of various cytokines as well as the extent of MHC-I expression. However, research exploring the combined effects of inflammation and zinc deficiency remains limited. One of the primary challenges in investigating the influence of zinc status on cytokine production is the specificity of the cell types utilized in experimental settings. This study investigates zinc depletion and inflammation using THP-1 monocytes as an model, with HIV-1 viral peptide pools and TPEN (,,' ,'-Tetrakis (2-pyridylmethyl) ethylenediamine), an intracellular zinc chelator. Zinc depletion was confirmed through the application of zinquin ethyl ester fluorescence microscopy. Additionally, we assessed the expression of zinc transporters, Bcl2 family proteins, and caspase-3 using quantitative RT-PCR and Western blot analyses. The production of TNF-α was evaluated through Golgi-Stop experiments, while MHC-I levels were measured following an 8 h incubation with HIV-1 viral peptides. The impact of PHA on monocytes concerning cytokine production and MHC-I levels was also examined. Our results revealed a rapid increase in TNF-α production and elevated MHC-I levels within 8 h post-stimulation. Furthermore, we observed an enhancement of endoplasmic reticulum (ER) stress markers, including CHOP, ATF6, and PERK, as well as BCl2 family-related genes, following treatment with the peptide pool. These findings highlight the hyperactivation of monocytes in response to HIV-1 viral peptides, which may contribute to immune system impairment through caspase-mediated apoptosis.