Advances in the pharmacological management of hyperlipidemia through the use of combination therapies.

Introduction: Lipid-lowering therapies are well established for the treatment of cardiovascular disease (CVD). Historically monotherapy studies were performed but the introduction of statins has led to these drugs being recognized as baseline therapies and to the investigation of combination therapy of both older and newer medications with them.

Areas Covered: Surrogate marker studies have shown additive effects on LDL-C, triglycerides and HDL-C of combination therapies with statins and these have extended to lipoprotein (a).

ALSUntangled #77: Psilocybin.

ALSUntangled reviews alternate and off-label treatments prompted by patient interest. Here, we review psilocybin, a chemical derived from mushrooms and belonging in the category of drugs known as psychedelics. Psilocybin has plausible mechanisms for slowing ALS progression because of its ability to cross the blood brain barrier and effect neurogenesis and inflammation.

Computational Evaluation of Fusarium nygamai Compounds as AcrD Efflux Pump Protein Inhibitors of Salmonella Typhimurium.

In Salmonella Typhimurium, efflux pump proteins, such as AcrD actively expel drugs and hazardous chemicals from bacterial cells, resulting in treatment failure and the emergence of antibiotic-resistant variants. Focusing on AcrD may lead to the development of novel antimicrobials against multidrug-resistant bacteria. However, challenges persist in achieving high selectivity, low toxicity, and effective bacterial penetration.

Advancing Precision Therapy for Colorectal Cancer: Developing Clinical Indications for Multi-target Kinase Inhibitor BPR1J481 Using Patient-Derived Xenograft Models.

The large and rapid increase in the incidence and mortality of colorectal cancer (CRC) demonstrates the urgent need for new drugs with higher efficacy to treat CRC. However, the lack of applicable and reliable preclinical models significantly hinders the progress of drug development. Patient-derived xenograft (PDX) models are currently considered reliable in vivo preclinical models for predicting drug efficacy in cancer patients.

Pan-genome analysis and drug repurposing strategies for extensively drug-resistant Salmonella Typhi: Subtractive genomics and e-pharmacophore approaches.

In the current study, we presented the genome sequence and taxonomic classification of the new extensively drug-resistant (XDR) Salmonella enterica serovar Typhi strain JRCGR-ST-AK02. Its genome size was found to be 4,780,534 bp, containing 4864 genes. Taxonomic classification was performed based on the Average Nucleotide Identity (ANI), Genome-to-Genome Distance Calculator (GGDC) and Average Amino Acid Identity (AAI) analysis.

Redox/NIR dual-responsive glutathione extended polyurethane urea electrospun membranes for synergistic Chemo-Photothermal therapy.

Despite advancements in cancer treatments, therapies frequently exhibit high cytotoxicity, and surgery remains the predominant method for treating most solid tumors, often with limited success in preventing post-surgical recurrence. Implantable biomaterials, designed to release drugs at a localised site in response to specific stimuli, represent a promising approach for enhancing tumour therapy. In this study, a redox-responsive glutathione extended polyurethane urea (PolyCEGS) was used to produce paclitaxel (PTX) and gold nanorods (AuNRs) loaded electrospun membranes for combined redox/near-infrared (NIR) light-responsive release chemotherapy and hyperthermic effect.

Application of cyclodextrin-based metal-organic frameworks for multi-drug carriers: A combined experimental and simulation study.

Combination therapy using multiple drugs has the potential for synergistic therapeutic effects and reduction in the administered dose. Furthermore, when combined with a drug delivery system, the therapeutic agents can effectively be targeted and delivered to the affected area. Therefore, a single carrier capable of encapsulating multiple drugs is of clinical significance.

Exploring the role of pomalidomide in androgen-dependent prostate cancer: a computational analysis.

Prostate cancer (PC) is among the most prevalent cancers in males. It is the leading cause of death in men, in around 48 out of 185 countries. Increased androgen receptor (AR) activity is the key factor contributing to the development or progression of newly diagnosed cases of prostate cancer.

High-Throughput Microarray Approaches for Predicting the Stability of Drug-Polymer Solid Dispersions.

Amorphous solid dispersions (ASDs) offer a well-recognized strategy to improve the effective solubility and, hence, bioavailability of poorly soluble drugs. In this study, we developed an extensive library of a significant number of solid dispersion formulations using a library of chemically diverse drugs combined with a water-soluble polymer (polyvinylpyrrolidone vinyl acetate, PVPVA) at different loadings. These formulations were printed as microarrays of solid dispersion formulations, utilizing minimal material amounts (nanograms).

Anti-wrinkle activity of the ethanol extract of Aronia melanocarpa for development of the cosmeceutical ingredients.

Despite the abundance of natural biological resources in Aronia melanocarpa, there is still insufficient research specifically exploring the potential for developing cosmeceutical compositions utilizing this plant. To develop the ingredient with the cosmeceutical function, the anti-wrinkle effect of the ethanol extract of A. melanocarpa was investigated.

Influence of Azadirachta indica leaf extracts on tumor necrosis factor-α and interleukin-6 in albino rats and its computational analysis.

The current study was designed to investigate the effect of A. indica (Neem) leaf extracts (ethanolic and aqueous) in yeast-induced pyrexia and acetic acid-induced writhing in rat models to evaluate the antipyretic and analgesic biomarkers and its phytochemical screening with computational analysis. For the antipyretic activity model 60 albino rats (160-200g) of either sex were divided into 4 groups and all groups were injected with yeast to induce pyrexia.

Recent Progress of Substituted Allylboron Compounds in Catalytic Asymmetric Allylation Reactions.

The catalytic asymmetric allylation reaction involving allylboron species has emerged as a powerful tool to access highly stereoselective allylation products. In the early years, most of the researches focused on the reaction of unsubstituted allylboronates with ketones or imines. With the synthesis of complex substituted allylboronates, allylboronic acids and allyltrifluoroborates, the type of reactions and the variety of substrates are greatly expanded.

A Supramolecular-Quantum Dot System for Broad-Spectrum Detection of Fentanyl Analogs.

Synthetic opioids, especially fentanyl and its analogs, have created an epidemic of abuse and significantly increased overdose deaths in the United States. Current detection methods have drawbacks in their sensitivity, scalability, and portability that limit field-based application to promote public health and safety. The need to detect trace amounts of fentanyl in complex mixtures with other drugs or interferents, and the continued emergence of new fentanyl analogs, further complicates detection.

Interface-aware molecular generative framework for protein-protein interaction modulators.

Protein-protein interactions (PPIs) play a crucial role in numerous biochemical and biological processes. Although several structure-based molecular generative models have been developed, PPI interfaces and compounds targeting PPIs exhibit distinct physicochemical properties compared to traditional binding pockets and small-molecule drugs. As a result, generating compounds that effectively target PPIs, particularly by considering PPI complexes or interface hotspot residues, remains a significant challenge.

Resistant starch grafted cerium-sulfasalazine infinite coordination polymers synergistically remold intestinal metabolic microenvironment for inflammatory bowel disease therapy.

Inflammatory bowel disease (IBD) is a chronic gastrointestinal disease which is closely related with the overproduced reactive oxygen species (ROS), increased pro-inflammatory cytokines and disordered intestinal microbes. However, current therapeutic methods usually ignored the interrelation among the pathogenesis, and mainly focused on a single factor, inducing clinical outcomes unsatisfied. Herein, biocompatible infinite coordination polymers of drugs (Ce-SASP-RS ICPs) composed of Ce ions, FDA-approved drug sulfasalazine (SASP) and natural ingredient resistant starch (RS) were developed for synergistic treatment of IBD.

Efficient analysis of drug interactions in liver injury: a retrospective study leveraging natural language processing and machine learning.

Background: Liver injury from drug-drug interactions (DDIs), notably with anti-tuberculosis drugs such as isoniazid, poses a significant safety concern. Electronic medical records contain comprehensive clinical information and have gained increasing attention as a potential resource for DDI detection. However, a substantial portion of adverse drug reaction (ADR) information is hidden in unstructured narrative text, which has yet to be efficiently harnessed, thereby introducing bias into the research.

HuR inhibition overcomes cFLIP-mediated doxorubicin resistance in triple-negative breast cancer.

Triple-negative breast cancer (TNBC) presents therapeutic challenges due to limited targeted treatment options and resistance to chemotherapy drugs, such as doxorubicin. This study investigated doxorubicin resistance mechanisms and a strategy to overcome it. A doxorubicin-resistant cell subline (231-DR) was developed from MDA-MB-231 TNBC cells, and enhanced expression of cellular FLICE-inhibitory protein (cFLIP) in 231-DR cells was identified as a potential driver of the resistance.

Integrated NMR-crystallography-computational approach for molecular recognition studies of human Gαi3 protein by a small molecule inhibitor.

The small molecule IGGi-11 targets Gαi subunits of heterotrimeric guanine nucleotide-binding proteins. Gα subunits are activated by G-protein-coupled receptors in response to extracellular stimuli by accelerating the exchange of GDP for GTP, but they are also activated by intracellular proteins like GIV, of which elevated levels correlate with increased cell migration and cancer metastasis. IGGi-11 disrupts the interaction of Gαi proteins with GIV and inhibits pro-invasive traits of metastatic breast cancer cells without interfering with GPCR signaling.

Development of axitinib-loaded polymeric ocular implants for the treatment of posterior ocular diseases.

Diabetic retinopathy (DR) and age-related macular degeneration (AMD) are the primary causes of vision impairment and blindness worldwide. The current treatment for these diseases is an intravitreal injection of anti-VEGF agents, which are costly and require frequent injections. Implants can be used to sustain the release of drugs and minimize side effects.

D-aring to explore: New approaches to gasdermin D targeting.

Novel inhibitors of pyroptosis promise breakthroughs in treating inflammatory diseases and malignant tumors. In this issue of Cell Chemical Biology, Hu et al. identify two repurposed drugs that selectively target gasdermin D (GSDMD) oligomers, effectively suppressing pyroptosis while reducing off-target effects typical of cysteine-based inhibitors.

Engineered DR/NIR dual-emission carbonized polymer dots for simultaneous tracking of lipid droplets and lysosomes.

Developing near-infrared fluorescent probes for simultaneous tracking of lipid droplets (LDs) and lysosomes is highly desirable for studying cell metabolism. In this work, deep-red/near-infrared dual-emission carbonized polymer dots (DN-CPDs) were prepared for ratiometric monitoring of the intracellular polarity. Detailed structural analysis revealed that the deep-red emission and near-infrared peak of DN-CPDs originate from the molecular state and surface state, respectively.

Advanced oral breviscapine sustained-release tablets for improved ischemic stroke treatment.

This study aimed to address the challenges associated with the low oral bioavailability and the necessity for frequent dosing of breviscapine (BRE), a mainstream drug in the treatment of cardiovascular and cerebrovascular diseases. The poor solubility and permeability of BRE in the gastrointestinal tract were identified as significant barriers to effective drug absorption, thereby impacting therapeutic efficacy and patient compliance. To enhance the gastrointestinal absorption of BRE, particles loaded with BRE were engineered utilizing Cremophor EL (CrEL), an absorption enhancer, in conjunction with mesoporous silica, a biocompatible drug delivery vector, formulating mesoporous silica particles loaded with BRE and CrEL (BRE-CrEL@SiO).

Non-targeted screening of illegal added hypoglycemic drugs and their derivatives in functional foods using characteristic fragment ions scanning based on liquid chromatography-high-resolution mass spectrometry.

Functional foods that are illegally adulterated with chemical hypoglycemic drugs or their derivatives pose serious risks to human health. However, the detection of these compounds is a challenge due to the unknown nature of their structures, particularly as many of these compounds are newly synthesized and lack standardized references. In this study, we developed a non-targeted screening strategy for detecting illegally added hypoglycemic drugs and their derivatives in oral solution and hard capsule functional foods.

Metabologenomics-Driven Discovery of Nocardimicins from a Psychrophilic sp. Strain.

A combined strategy of 2D-NMR-metabolomics-driven substructure tracking with genome mining led to the targeted discovery of 10 nocobactin-type lipopeptides (-) from the Arctic-derived phychrophillic sp. L-016, among which - are new compounds, named nocardimicins S-W. The phenoxazole moiety in -, featuring unique NMR values and correlations, was used as a probe for tracking nocardimicin analogues.

Single-Vesicle Electrochemistry in Fresh Brain Slices Enables In Situ Quantification of Vesicular Monoamine.

The quantitative analysis of vesicular neurotransmitters in neurons in situ is paramount for investigating neurodegenerative disorders, such as Alzheimer's disease and Parkinson's disease (PD). Unfortunately, a direct approach for monitoring neurotransmitter chemistry in single vesicles in fresh brain tissue has remained inaccessible so far. Here, we introduce an innovative platform of single-vesicle electrochemistry (SVE) in fresh brain tissue, enabling the quantification of neurotransmitters at the single-vesicle level for both soma and varicosity.