Target fishing and mechanistic insights of the natural anticancer drug candidate chlorogenic acid.

Chlorogenic acid (CGA) is a natural product that effectively inhibits tumor growth, demonstrated in many preclinical models, and phase II clinical trials for patients with glioma. However, its direct proteomic targets and anticancer molecular mechanisms remain unknown. Herein, we developed a novel bi-functional photo-affinity probe PAL/CGA and discovered mitochondrial acetyl-CoA acetyltransferase 1 (ACAT1) was one of the main target proteins of CGA by using affinity-based protein profiling (AfBPP) chemical proteomic approach.

PKC inhibitors promote breast cancer immune evasion by maintaining PD-L1 stability.

Protein kinase C (PKC) regulates diverse biological functions of cancer cells and is a promising therapeutic target. However, clinical trials of PKC-targeted therapies have not yielded satisfactory results. Recent studies have also indicated a tumor-suppressive role of PKCs unclear molecular mechanisms.

Spatial metabolomics highlights metabolic reprogramming in acute myeloid leukemia mice through creatine pathway.

Acute myeloid leukemia (AML) is recognized as an aggressive cancer that is characterized by significant metabolic reprogramming. Here, we applied spatial metabolomics to achieve high-throughput, in situ identification of metabolites within the liver metastases of AML mice. Alterations at metabolite and protein levels were further mapped out and validated by integrating untargeted metabolomics and proteomics.

SIRT3 differentially regulates lysine benzoylation from SIRT2 in mammalian cells.

Lysine benzoylation (Kbz), a new type of protein post-translational modification (PTM) we discovered, has garnered significant attention. While we initially identified SIRT2 as a debenzoylase in mammalian cells, recent findings suggest its exclusivity may be questioned. However, other debenzoylases in mammalian cells remain underexplored.

Novel virulence determinants in VP1 regulate the assembly of enterovirus-A71.

Unlabelled: Enterovirus-A71 (EV-A71) is the second most common causative agent after coxsackievirus A16 of hand, foot, and mouth disease. The capsids of EV-A71 consist of 60 copies of each of the four viral structural proteins (VP1-VP4). VP1 is highly exposed and surface accessible, playing a central role in virus particle assembly, attachment, and entry.

Inflammatory markers correlate with lymphocytes infiltrating and predict immunotherapy prognosis for esophageal cancer.

To investigate the prognostic value of inflammatory markers in esophageal squamous cell carcinoma (ESCC) patients treated with immune checkpoint inhibitors (ICIs). The infiltration of CD3 and CD8 T cells in tissue microarrays from 180 patients who underwent radical esophagectomy was detected using immunohistochemistry. A separate cohort of 351 patients with metastatic/recurrent or unresectable ESCC treated with ICIs was enrolled for further investigation.

MGAT4A/Galectin9-Driven N-Glycosylation Aberration as a Promoting Mechanism for Poor Prognosis of Endometrial Cancer with TP53 Mutation.

Emerging evidence recognizes aberrant glycosylation as the malignant characteristics of cancer cells, but little is known about glycogenes' roles in endometrial carcinoma (EC), especially the most aggressive subtype carrying TP53 mutations. Using unsupervised hierarchical clustering, an 11-glycogene cluster is identified to distinguish an EC subtype associated with frequent TP53 mutation and worse prognosis. Among them, MGAT4A (alpha-1,3-mannosyl-glycoprotein 4-β-N-acetylglucosaminyltransferase A) emerges as the most consistently overexpressed glycogene, contributing to EC aggressiveness.

Rapid Liquid Chromatography-Tandem Mass Spectrometry Method for Determination of Total and Free Testosterone in Human Serum and Its Application to Monitoring Biomarker Response of Elite Athletes.

Total testosterone (TT) and free testosterone (FT) are important biochemical markers for anabolism of the human body, and can also serve as early screening indicators for overtraining syndrome (OTS). Presently, there is no fast and reliable serum TT and FT determination method in the field of sport science that can meet the requirements of sports research. Thus, a rapid and accurate determination method for serum TT and FT to fill the gap is needed urgently in sports training.

Raddeanin A suppresses intracellular Methylcytosine DNA modification engaged the metastasis of hepatocellular carcinoma.

Ethnopharmacological Relevance: The Anemonoides Raddeana (Rege) Holubhe is commonly employed in clinical practice as a traditional Chinese medicine for the treatment of conditions such as rheumatism and limb numbness. Raddeanin A (RA), an active compound derived from this Traditional Chinese Medicine (TCM), demonstrates specific anticancer properties against many tumorigeneses. However, the molecular mechanism underlying its effects on hepatocellular carcinoma (HCC) remains unexplored.

An automatic LC-MS/MS data analysis workflow for herbal compound annotation with AutoAnnotatoR: A case study of ten botanical origins of Fritillaria species.

Background: Despite the widespread implementation of analytical hardware capable of recording large-scale datasets for botanical natural products, the data processing procedures for compound annotation remain a bothersome obstacle that demand a tremendous amount of time and expert knowledge.

Methods: Herein, an automatic LC-MS/MS data analysis workflow with AutoAnnotatoR was introduced for the compound annotation of plant derived natural products, which has the merits of great efficiency, high accuracy, saving time and simplified process. This procedure enabled automatic matching of MS data with characteristic fragment ions, as well as MS data with compound libraries, which improves the accuracy of structural elucidation.

Polymethoxylated flavones for modulating signaling pathways in inflammation.

Aberrant signaling pathways play a crucial role in the pathogenesis of various diseases, including inflammatory disorders and autoimmune conditions. Polymethoxylated flavones (PMFs), a class of natural compounds found in citrus fruits, have obtained increasing attention for their potential therapeutic effects in modulating inflammatory responses. Although significant progress has been made in the pharmacological research of PMFs, the mechanisms by which they modulate signaling pathways to treat inflammation have not been systematically reviewed or analyzed.

Recent advances in the structures and bioactivities of benzopyrans derived from marine fungi: a review.

Marine fungi represent a treasure trove of bioactive secondary metabolites, with benzopyran compounds emerging as a significant class of these natural products. This review delves into the structural diversity, biological activities, and sources of benzopyran compounds, highlighting their isolation from marine fungi inhabiting diverse environments such as sponges, marine sediments, algae, mangroves, and corals. Our literature search, conducted from 2000 to 2023, has identified a wealth of benzopyran compounds, showcasing their potential as lead compounds in drug development.

Talaketides A-G, linear polyketides with prostate cancer cytotoxic activity from the mangrove sediment-derived fungus Talaromyces sp. SCSIO 41027.

Seven novel linear polyketides, talaketides A-G (1-7), were isolated from the rice media cultures of the mangrove sediment-derived fungus Talaromyces sp. SCSIO 41027. Among these, talaketides A-E (1-5) represented unprecedented unsaturated linear polyketides with an epoxy ring structure.

The biologically and ecologically important natural products from the Chinese sea hare Bursatella leachii: structures, stereochemistry and beyond.

A novel amide alkaloid, bursatamide A (1), featuring an unprecedented propyl-hexahydronaphthalene carbon framework, was isolated from the infrequently studied sea hare Bursatella leachi, alongside a new 3-phenoxypropanenitrile alkaloid, bursatellin B (2), and twelve known compounds. The structures of 1 and 2 were elucidated through comprehensive spectroscopic data analyses, while their relative and absolute configurations (ACs) were established through total synthesis and a series of quantum chemical calculations, including calculated electronic circular dichroism (ECD) spectra, optical rotatory dispersion (ORD) methods, and DP4+ probability analyses. Bursatamide A (1) demonstrated inhibitory effects against the human pathogenic bacteria Listeria monocytogenes and Vibrio cholerae.

Enhancement of oral bioavailability of celastrol by chitosan microencapsulated porous starch carriers.

Celastrol demonstrates significant potential in immunomodulatory applications; however, its low oral bioavailability presents a substantial obstacle to its clinical translation. Here, we combined porous starch with chitosan to develop an efficacious microencapsulation system aimed at enhancing the oral absorption of celastrol. Microcapsule carrier for celastrol was formulated Through the utilization of chitosan-coated porous starch particle technology and Subsequent evaluations of the morphology and release kinetics of microcapsules.

New perspective on central nervous system disorders: focus on mass spectrometry imaging.

An abnormally organized brain spatial network is linked to the development of various central nervous system (CNS) disorders, including neurodegenerative diseases and neuropsychiatric disorders. However, the complicated molecular mechanisms of these diseases remain unresolved, making the development of treatment strategies difficult. A novel molecular imaging technique, called mass spectrometry imaging (MSI), captures molecular information on the surface of samples .

Prediction of Multi-Pharmacokinetics Property in Multi-Species: Bayesian Neural Network Stacking Model with Uncertainty.

Pharmacokinetic (PK) properties of a drug are vital attributes influencing its therapeutic effectiveness, playing an important role in the drug development process. Focusing on the difficult task of predicting PK parameters, we compiled an extensive data set comprising parameters across multiple species. Building upon this groundwork, we introduced the PKStack ensemble model to predict PK parameters across diverse species.

Tilianin suppresses NLRP3 inflammasome activation in myocardial ischemia/reperfusion injury via inhibition of TLR4/NF-κB and NEK7/NLRP3.

Tilianin, a flavonoid compound derived from L., is recognized for its diverse biological functionalities, in particular alleviating myocardial ischemia-reperfusion injury (MIRI). There is ample evidence suggesting that the NLRP3 inflammasome has a significant impact on the development of MIRI.

Discovery of peptidomimetic spiropyrrolidine derivatives as novel 3CL inhibitors against SARS-CoV -2.

Given the high pathogenicity and rapid mutation rates of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), it is imperative to sustain efforts in drug research and development. Herein, we present the design, synthesis, and evaluation of peptidomimetic spiropyrrolidine derivatives as potent 3CL inhibitors against SARS-CoV-2. Among the synthesized derivatives, several compounds exhibited high potency in inhibiting 3CL, with IC values ranging from 21 nM to 53 nM.

Single Amine or Guanidine Modification on Norvancomycin and Vancomycin to Overcome Multidrug-Resistance through Augmented Lipid II Binding and Increased Membrane Activity.

Vancomycin and norvancomycin have diminished antibacterial efficacy due to acquired or intrinsic resistance from mutations in the terminal dipeptide of lipid II in Gram-positive bacteria or failure to penetrate into the periplasm in Gram-negative bacteria. Herein, we rationally designed and synthesized a series of vancomycin analogues bearing single amine or guanidine functionality, altering various linkers and modification sites, to combat the resistance. Extensive antibacterial screening was performed to delineate a comprehensive SAR.

Rhodium-Catalyzed C-H Arylation of Indoles with Arylsilanes at Room Temperature.

The Cp*Rh-catalyzed C-H arylation of indoles with arylsilanes is developed. This C-H activation transformation allows for the Rh-catalyzed indole C arylation to overcome the limitations of requiring strong directing group assistance and high-temperature conditions, achieving a room-temperature transformation driven by a weak directing group. Cp*Rh/MeOH catalytic media are considered a key factor enabling this transformation to occur under mild conditions, and experimental studies and theoretical calculations were performed to rationalize the reaction mechanisms and the influence of methanol as a solvent in promoting the reaction.

Design and Synthesis of Dual Galectin-3 and EGFR Inhibitors Against Liver Fibrosis.

Liver fibrosis, mainly arising from chronic viral or metabolic liver diseases, is a significant global health concern. There is currently only one FDA-approved drug (Resmetirom) in the market to combat liver fibrosis. Both galectin-3 and epidermal growth factor receptor (EGFR) play important roles in liver fibrosis, while galectin-3 may interact with EGFR.