MicroRNAs (miRNAs) are small non-coding RNAs that regulate gene expression by binding to the 3'-untranslated regions of target mRNAs, influencing various biological processes at the post-transcriptional level. Identifying miRNA transcription start sites (TSSs) and transcription factors' (TFs) regulatory roles is crucial for elucidating miRNA function and transcriptional regulation. miRStart 2.
View Article and Find Full Text PDFMicroRNAs (miRNAs) are small non-coding RNAs (18-26 nucleotides) that regulate gene expression by interacting with target mRNAs, affecting various physiological and pathological processes. miRTarBase, a database of experimentally validated miRNA-target interactions (MTIs), now features over 3 817 550 validated MTIs from 13 690 articles, significantly expanding its previous version. The updated database includes miRNA interactions with therapeutic agents, revealing roles in drug resistance and therapeutic strategies.
View Article and Find Full Text PDFBackground Aims: Liver fibrosis is characterized by the progressive scarring of liver tissue. Oxidative stress is a critical causal factor of hepatic stellate cell (HSC) activation and the subsequent liver fibrogenesis, but the mechanism is not fully understood. Cysteine sulfinic acid (Cys-SO2H), a modification of reactive cysteine residues, is a unique form of oxidative response that alters the structure and function of proteins.
View Article and Find Full Text PDFCancer is a severe illness that significantly threatens human life and health. Anticancer peptides (ACPs) represent a promising therapeutic strategy for combating cancer. In silico methods enable rapid and accurate identification of ACPs without extensive human and material resources.
View Article and Find Full Text PDFBackground: Additional resection for invasive cancer at perihilar cholangiocarcinoma (pCCA) resection margins has become a consensus. However, controversy still exists regarding whether additional resection is necessary for residual biliary intraepithelial neoplasia (BilIN).
Method: Consecutive patients with pCCA from two hospitals were enrolled.
Antiviral peptides (AVPs) have shown potential in inhibiting viral attachment, preventing viral fusion with host cells and disrupting viral replication due to their unique action mechanisms. They have now become a broad-spectrum, promising antiviral therapy. However, identifying effective AVPs is traditionally slow and costly.
View Article and Find Full Text PDFScramblase Xk-related protein 8 (Xkr8) regulates the externalization of phosphatidylserine (PS) during apoptosis and holds a pivotal role in fostering tumor immunosuppression. Targeting Xkr8 in conjunction with chemotherapy demonstrated a novel avenue for amplifying antitumor immune response and overcoming chemo-immune resistance. Here we further evaluated this strategy by using a clinically relevant orthotopic model and elucidated the mechanism through in-depth single-cell RNA sequencing (scRNA-seq).
View Article and Find Full Text PDFBackground: Potato virus Y (PVY) is a prominent representative of plant viruses. It can inflict severe damage upon Solanaceae plants, leading to global dissemination and substantial economic losses. To discover new antiviral agents, a class of planar chiral thiourea molecules through the key step of N-heterocyclic carbene-catalyzed nitrile formation reaction was synthesized with excellent optical purities for antiviral evaluations against plant virus PVY.
View Article and Find Full Text PDFKinases as important enzymes can transfer phosphate groups from high-energy and phosphate-donating molecules to specific substrates and play essential roles in various cellular processes. Existing algorithms for kinase activity from phosphorylated proteomics data are often costly, requiring valuable samples. Moreover, methods to extract kinase activities from bulk RNA sequencing data remain undeveloped.
View Article and Find Full Text PDF(PVY) is an important plant virus that has spread worldwide, causing significant economic losses. To search for novel structures as potent antiviral agents, a series of chiral indole derivatives containing oxazoline moieties were designed and synthesized and their anti-PVY activities were evaluated. Biological activity tests demonstrated that many chiral compounds exhibited promising anti-PVY activities and that their absolute configurations exhibited obvious distinctions in antiviral bioactivities.
View Article and Find Full Text PDFPARP inhibitors (PARPi)-based synthetic lethal therapy demonstrates limited efficacy for most cancer types that are homologous recombination (HR) proficient. To potentiate the PARPi application, a nanocarrier based on 5-azacytidine (AZA)-conjugated polymer (PAZA) for the codelivery of AZA and a PARP inhibitor, BMN673 (BMN) is developed. AZA conjugation significantly decreased the nanoparticle (NP) size and increased BMN loading.
View Article and Find Full Text PDFN-Heterocyclic carbenes (NHCs) catalysts have been employed as effective tools in the development of various reactions, which have made notable contributions in developing diverse reaction modes and generating significant functionalized molecules. This review provides an overview of the recent advancements in the chemo- and regioselective activation of different aldehydes using NHCs, categorized into five parts based on the different activation modes. A brief conclusion and outlook is provided to stimulate the development of novel activation modes for accessing functional molecules.
View Article and Find Full Text PDFThe multifaceted chemo-immune resistance is the principal barrier to achieving cure in cancer patients. Identifying a target that is critically involved in chemo-immune-resistance represents an attractive strategy to improve cancer treatment. iRhom1 plays a role in cancer cell proliferation and its expression is negatively correlated with immune cell infiltration.
View Article and Find Full Text PDFBackground: Nonearly biliary complications (BCs) after liver transplantation (LT) are highly associated with immunological status. Tacrolimus is the main immunosuppressant. Whether and how tacrolimus bioavailability affects BCs is unclear.
View Article and Find Full Text PDFObjectives: To analyze the distribution characteristics of Traditional Chinese Medicine (TCM) syndromes in patients with oxaliplatin-induced peripheral neuropathy (OIPN) and observe the clinical efficacy of Bushen Yiqi formula (, BSYQF) in treating patients with OIPN.
Methods: A total of 89 patients with OIPN were enrolled in this study. The TCM syndrome characteristics were investigated by frequency analysis methodology after collecting and analyzing the TCM syndrome elements of the patients with the OIPN TCM syndrome element scale.
Drug-target interactions (DTIs) are considered a crucial component of drug design and drug discovery. To date, many computational methods were developed for drug-target interactions, but they are insufficiently informative for accurately predicting DTIs due to the lack of experimentally verified negative datasets, inaccurate molecular feature representation, and ineffective DTI classifiers. Therefore, we address the limitations of randomly selecting negative DTI data from unknown drug-target pairs by establishing two experimentally validated datasets and propose a capsule network-based framework called CapBM-DTI to capture hierarchical relationships of drugs and targets, which adopts pre-trained bidirectional encoder representations from transformers (BERT) for contextual sequence feature extraction from target proteins through transfer learning and the message-passing neural network (MPNN) for the 2-D graph feature extraction of compounds to accurately and robustly identify drug-target interactions.
View Article and Find Full Text PDFEthnopharmacological Relevance: Sophorae Flavescentis Radix (Kushen) is the primary herb component of Compound Kushen Injection (CKI), an approved clinical treatment for tumors. Despite CKI's widespread use, the underlying mechanisms of Kushen regarding microRNA-target and pathway remain unclear in non-small cell lung cancer (NSCLC).
Aim Of The Study: This study aimed to elucidate the crucial miRNAs-targets and pathways responsible for the Kushen's impact on NSCLC.