Calycosin-7-O-β-D-Glucoside Ameliorates Palmitate-Induced Lipid Accumulation in HT22 Cells.

Background: The pathogenesis of Alzheimer's disease (AD) is complex. Recent research suggests that AD patients have early disorders in brain cholesterol metabolism. Cholesterol and its derivatives accumulate in neurons, leading to p-Tau overproduction and synaptic dysfunction, initiating AD progression.

Speciation distribution and leaching behavior of heavy metals in coal gasification fine ash: Influence of particle size, carbon content and mineral composition.

In this study, the occurrence and distribution of heavy metals in coal gasification fine ash (CGFA) with different particle sizes were investigated to ensure safer disposal and utilization strategies for CGFA. These measures are critical to sustainable industrial practices. This study investigates the distribution and leachability of heavy metals in CGFA, analyzing how these factors vary with particle size, carbon content, and mineral composition.

Lipoxin A ameliorates knee osteoarthritis progression in rats by antagonizing ferroptosis through activation of the ESR2/LPAR3/Nrf2 axis in synovial fibroblast-like synoviocytes.

Background: Our previous studies have shown that lipoxin A (LXA) can serve as a potential biomarker for assessing the efficacy of exercise therapy in knee osteoarthritis (KOA), and fibroblast-like synoviocytes (FLSs) may play a crucial role in KOA pain as well as in the progression of the pathology.

Objective: By analyzing the GSE29746 dataset and collecting synovial samples from patients with different Kellgren-Lawrence (KL) grades for validation, we focused on exploring the potential effect of LXA on ferroptosis in FLSs through the ESR2/LPAR3/Nrf2 axis to alleviate pain and pathological advancement in KOA.

Methods: The association between FLSs ferroptosis and chondrocyte matrix degradation was explored by cell co-culture.

Sustainable building materials-recycled aggregate and concrete: a systematic review of properties, modification techniques, and environmental impacts.

Resource utilization of construction and demolition (C&D) waste has great potential to significantly reduce the consumption of natural resources and improve the environment. Meanwhile, establishing a sound policy system and reducing production are the key ways to solve the problem of C&D waste. Numerous studies on C&D waste, recycled concrete aggregate (RA), and recycled aggregate concrete (RAC) have been reported in the literature, with few systematic summaries.

Targeting ENPP1 for cancer immunotherapy: Killing two birds with one stone.

Cancer immunotherapy, particularly with immune checkpoint inhibitors, has revolutionized the paradigm of cancer treatment. Nevertheless, the efficacy of cancer immunotherapy remains limited in most clinical settings due to the lack of a preexisting antitumor T-cell response in tumors. Therefore, the clinical outcomes of cancer immunotherapy must be improved crucially.

Study on the relation between macro-mechanical properties and micro-structure of geopolymers with different activator modulus.

The fly ash-based geopolymer (FABG) containing slag has distinct advantages in field applications. In this work, given that the activator modulus is a significant parameter affecting the properties of FABG, the influence mechanism of activator modulus (SiO/NaO from 1.1 to 1.

[Mechanism of albiflorin in improvement of Alzheimer's disease based on network pharmacology and in vitro experiments].

This study aimed to explore the mechanism of albiflorin in the treatment of Alzheimer's disease(AD) based on network pharmacology, molecular docking, and in vitro experiments. Network pharmacology was used to predict the potential targets and pathways of albiflorin against AD, and molecular docking technology was used to verify the binding affinity of albiflorin to key target proteins. Finally, the AD cell model was induced by Aβ_(25-35) in rat pheochromocytoma(PC12) cells and intervened by albiflorin to validate core targets and pathways.

[Serum metabolomics study of Psoraleae Fructus in improving learning and memory ability of APP/PS1 mice].

This study aimed to investigate the mechanism of Psoraleae Fructus in improving the learning and memory ability of APP/PS1 mice by serum metabolomics, screen the differential metabolites of Psoraleae Fructus on APP/PS1 mice, and reveal its influence on the metabolic pathway of APP/PS1 mice. Thirty 3-month-old APP/PS1 mice were randomly divided into a model group and a Psoraleae Fructus extract group, and another 15 C57BL/6 mice of the same age were assigned to the blank group. The learning and memory ability of mice was evaluated by the Morris water maze and novel object recognition tests, and metabolomics was used to analyze the metabolites in mouse serum.

Polylactic-co-glycolic acid-based nanoparticles modified with peptides and other linkers cross the blood-brain barrier for targeted drug delivery.

Because of the blood-brain barrier, only a limited fraction of drugs can penetrate the brain. As a result, there is a need to take larger doses of the drug, which may result in numerous undesirable side effects. Over the past few decades, a plethora of research has been conducted to address this issue.

Long non-coding RNAs in osteoporosis: from mechanisms of action to therapeutic potential.

Osteoporosis is a clinical disease characterized by decreased bone density due to a disrupted balance between bone formation and resorption, which increases fracture risk and negatively affects the quality of life of a patient. LncRNAs are RNA molecules over 200 nucleotides in length with non-coding potential. Many studies have demonstrated that numerous biological processes involved in bone metabolism are affected.

Ginsenoside Compound K Ameliorates Osteoarthritis by Inhibiting the Chondrocyte Endoplasmic Reticulum Stress-Mediated IRE1α-TXNIP-NLRP3 Axis and Pyroptosis.

Osteoarthritis (OA) is a common joint disease, and studies have reported that the endoplasmic reticulum stress (ERS) in chondrocytes caused by the cartilage tissue damage could mediate the activation of Nod-like receptor protein 3 (NLRP3) inflammasomes through inositol-requiring enzyme 1 alpha (IRE1α) and thioredoxin interacting protein (TXNIP). Ginsenoside compound K (CK) has an inhibitory effect on IRE1α activation. However, the role of IRE1α-TXNIP and its interaction with CK are still unclear.

Targeting STING for cancer immunotherapy: From mechanisms to translation.

Cancer immunotherapy with immune checkpoint inhibitors has achieved unprecedented success in cancer treatment; However, only a subset of patients achieved clinical benefit from this treatment, underscoring the urgent need to identify new strategies to enhance the clinical efficacy of immune checkpoint inhibitors. Given the essential role of innate immunity in cancer immune surveillance, tremendous effort has been focused on the innate immune pathways that can be pharmacologically modulated to improve the clinical outcome of checkpoint inhibitors. The cyclic GMP-AMP synthase (cGAS)-stimulator of interferon genes (STING) signaling pathway plays essential roles in host defense against cancers.

Integrative modeling of the cell.

A whole-cell model represents certain aspects of the cell structure and/or function. Due to the high complexity of the cell, an integrative modeling approach is often taken to utilize all available information including experimental data, prior knowledge and prior models. In this review, we summarize an emerging workflow of whole-cell modeling into five steps: (i) gather information; (ii) represent the modeled system into modules; (iii) translate input information into scoring function; (iv) sample the whole-cell model; (v) validate and interpret the model.

Bayesian metamodeling of complex biological systems across varying representations.

Comprehensive modeling of a whole cell requires an integration of vast amounts of information on various aspects of the cell and its parts. To divide and conquer this task, we introduce Bayesian metamodeling, a general approach to modeling complex systems by integrating a collection of heterogeneous input models. Each input model can in principle be based on any type of data and can describe a different aspect of the modeled system using any mathematical representation, scale, and level of granularity.

Design, synthesis and biological evaluation of pyrazolo[3,4-]pyridazinone derivatives as covalent FGFR inhibitors.

Fibroblast growth factor receptors (FGFRs) have emerged as promising targets for anticancer therapy. In this study, we synthesized and evaluated the biological activity of 66 pyrazolo[3,4-]pyridazinone derivatives. Kinase inhibition, cell proliferation, and whole blood stability assays were used to evaluate their activity on FGFR, allowing us to explore structure-activity relationships and thus to gain understanding of the structural requirements to modulate covalent inhibitors' selectivity and reactivity.

Folic Acid and Poly(ethylene glycol) Decorated Paclitaxel Nanocrystals Exhibit Enhanced Stability and Breast Cancer-Targeting Capability.

In part because of their high drug loading, nanocrystals (NCs) have seen extensive use in drug delivery, particularly for insoluble or poorly soluble drugs. It remains a challenge, however, to prepare stable nanocrystals with tumor-targeting capability. Here, we designed a novel preparation of stable paclitaxel (PTX) nanocrystals with efficient active tumor-targeting properties.

DrugSpaceX: a large screenable and synthetically tractable database extending drug space.

One of the most prominent topics in drug discovery is efficient exploration of the vast drug-like chemical space to find synthesizable and novel chemical structures with desired biological properties. To address this challenge, we created the DrugSpaceX (https://drugspacex.simm.

Bioactivity Prediction Based on Matched Molecular Pair and Matched Molecular Series Methods.

Background: Enhancing a compound's biological activity is the central task for lead optimization in small molecules drug discovery. However, it is laborious to perform many iterative rounds of compound synthesis and bioactivity tests. To address the issue, it is highly demanding to develop high quality in silico bioactivity prediction approaches, to prioritize such more active compound derivatives and reduce the trial-and-error process.

Revisiting Aldehyde Oxidase Mediated Metabolism in Drug-like Molecules: An Improved Computational Model.

Aldehyde oxidase (AOX) is a drug metabolizing molybdo-flavoenzyme that has gained increasing attention because of contribution to the biotransformation in phase I metabolism of xenobiotics. Unfortunately, the intra- and interspecies variations in AOX activity and lack of reliable and predictive animal models make evaluation of AOX-catalyzed metabolism prone to be misleading. In this study, we developed an improved computational model integrating both atom-level and molecule-level features to predict whether a drug-like molecule is a potential human AOX (hAOX) substrate and to identify the corresponding sites of metabolism.

Percutaneous absorption and brain distribution facilitation of borneol on tetramethylpyrazine in a microemulsion-based transdermal therapeutic system.

In this study, we show that the percutaneous absorption and brain distribution of tetramethylpyrazine (TMP) is enhanced when combined with borneol (BN) in a microemulsion-based transdermal therapeutic system (ME-TTS). The formulation of the TMP and BN microemulsion (TEM-BN-ME) was optimized in skin permeation studies following a uniform experimental design. Male Sprague-Dawley rats were used for the pharmacokinetic and tissue distribution studies of TMP-BN-ME-TTS.

Diterpenoids from the Root Bark of and Evaluation of Their Phosphodiesterase Type 4D Inhibitory Activity.

Thirty-two diterpenoids were obtained from the root bark of , and, among them, five compounds (pinmassins A-E) were identified as undescribed analogues. Spectroscopic methods, X-ray single-crystal diffraction analysis, and ECD calculations were applied to establish the structure of the new isolates. Pinmassin D () and abieta-8,11,13,15-tetraen-18-oic acid () showed moderate phosphodiesterase type 4D (PDE4D) inhibitory effects with IC values of 2.

Increased microneedle-mediated transdermal delivery of tetramethylpyrazine to the brain, combined with borneol and iontophoresis, for MCAO prevention.

The aim of this research was to improve transdermal delivery and distribution of tetramethylpyrazine (TMP) in the brain, by adding borneol (BN) and iontophoresis (ITP), and using microneedles (MN), to prevent middle cerebral artery occlusion (MCAO). BN was encapsulated into sulfobutylated-β-cyclodextrin (BN-SBE-β-CD), and then dispersed together with TMP. Four delivery groups were tested: passive (with no ITP and MN), ITP, MN, and MN combined with ITP (MN-ITP).

Novel nanostructured lipid carriers-loaded dissolving microneedles for controlled local administration of aconitine.

Nanostructured lipid carriers (NLCs) can enhance the safe transdermal delivery system of drugs. Moreover, dissolving microneedles (MNs) can enhance the permeability and controlled drug release. In this study, NLCs were formulated as a suitable vehicle for aconitine (ACO) delivery to effectively inhibit the inflammation of fibroblast-like synoviocytes isolated from a rat model of adjuvant-induced arthritis (AA-FLS).

Construction and in vitro and in vivo evaluation of folic acid-modified nanostructured lipid carriers loaded with paclitaxel and chlorin e6.

Breast cancer remains a major threat to women's health, and the incidence of breast cancer continues to increase each year. Paclitaxel (PTX) is commonly used to treat breast cancer, but shows limited solubility and is associated with major side effects, limiting its clinical applications. Photodynamic therapy (PDT) is a promising treatment for breast cancer but is limited by the poor solubility of photosensitizers and difficulties in targeting and enriching the tumor tissue with photosensitizers.

KinomeX: a web application for predicting kinome-wide polypharmacology effect of small molecules.

Motivation: The large-scale kinome-wide virtual profiling for small molecules is a daunting task by experimental and traditional in silico drug design approaches. Recent advances in deep learning algorithms have brought about new opportunities in promoting this process.

Results: KinomeX is an online platform to predict kinome-wide polypharmacology effect of small molecules based solely on their chemical structures.