Lithium Coupled with C6-Carboxyl Improves the Efficacy of Oligoguluronate in DSS-Induced Ulcerative Colitis in C57BL/6J Mice.

Oligoguluronate lithium (OGLi) was prepared for the purpose of enhancing the anti-ulcerative colitis (UC) activities of OG, in which lithium (Li) is coupled with the C6-carboxyl of G residue. The therapeutic effects of OGLi on dextran sulfate (DSS)-induced UC mice were investigated, and oligoguluronate sodium (OGNa) and lithium carbonate (LC) were used as contrasts. The effects of OGLi, OGNa and LC on the treatment of UC mice were studied by monitoring body weight change and evaluating colon length, the disease activity index (DAI), histopathological examination and gut microbiota regulation.

Identification of targets and comparative study of administration methods for the lipid-lowering effects of fucoidan from Saccharina japonica.

The lipid-lowering activity of fucoidan has been widely reported, but the exploration of its mechanisms is relatively limited, and studies on its direct targets are even scarcer. Additionally, it is unclear whether different administration methods affect the lipid-lowering activity of fucoidan. In current study, we used fucoidan derived from Saccharina japonica (SJF) to investigate its targets.

Heterologous Expression of Type II PKS Gene Cluster Leads to Diversified Angucyclines in J1074.

Heterologous expression has emerged as an effective strategy in activating cryptic gene clusters or improving yield. Eight compounds were successfully obtained by heterologous expression of the type II PKS gene cluster derived from marine sp. HDN155000 in the chassis host J1074.

P-selectin-targeted Polyguluronate sulfate-copper peroxide Nanomicelles for Chemodynamic therapy of breast Cancer.

The exploration of efficient and safe chemodynamic therapy (CDT)-based cancer treatment is expected but still faces challenges. Herein, a kind of multifunctional nanomicelles was constructed for CDT, combined with biocompatible polysaccharides as nanocarriers, pH responsiveness and active targeting of P-selectin overexpressed tumors. The P-selectin-targeted ligand, polyguluronate sulfate (PGS), complexed with copper peroxide to form PGS-Cu nanomicelles by electrostatic interactions.

Enzymatically extracted ulvans restrict viruses via STING signaling and type I interferon after cellular entry.

Ulvans, abundant natural polysaccharides produced by Ulvales, have been recognized for antiviral activities, though the underlying mechanisms are not fully understood. In this study, we focused on two polysaccharides and one oligosaccharide, which were extracted enzymatically from Ulva prolifera and named as PR1 (13.5 kDa), PR2 (7.

Spirophosphine-Catalyzed Enantioselective [3 + 2] Cycloaddition of Allenoates and Unsaturated α-Ketimine Esters.

A novel chiral spiro-monophosphine, OUC-Phos, was synthesized and utilized for the first time in the asymmetric Lu's [3 + 2] cycloaddition reaction of β,γ-unsaturated α-ketimine ester with allenoate. OUC-Phos, featuring a 3,3'-diphenyl-modified spirobiindane skeleton, demonstrated exceptional catalytic efficiency in the [3 + 2] cycloaddition to achieve high yields, enantioselectivities, and diastereoselectivities for the targeted products. The broad substrate scope encompassing diverse functional groups demonstrated the versatility of this methodology.

Discovery of novel nitrofuran PROTAC-like compounds as dual inhibitors and degraders targeting STING.

Aberrant activation of the innate immune molecule STING can initiate inflammation and autoimmune diseases. Small molecule inhibitors targeting STING have demonstrated therapeutic efficacy against these conditions. Moreover, employing degradants to target STING represents a novel approach to drug design strategy.

Polysaccharide- and protein-based hydrogel dressings that enhance wound healing: A review.

Hydrogels can possess desired biochemical and mechanical properties, excellent biocompatibility, satisfactory biodegradability, and biological capabilities that promote skin repair, making them ideal candidates for skin healing dressings. Polysaccharides, such as chitosan, hyaluronic acid and sodium alginate as well as proteins, including gelatin, collagen and fibroin proteins, are biological macromolecules celebrated for their biocompatibility and biodegradability, are at the forefront of innovative hydrogel dressing development. This work first summarizes the skin wound healing process and its influencing factors, and then systematically articulates the multifunctional roles of hydrogels based on biological macromolecules (polysaccharides and proteins) as dressing in addressing bacterial infection, hemorrhage and inflammation during wound healing.

Biosynthesis of Atypical Angucyclines Unveils New Ring Rearrangement Reactions Catalyzed by Flavoprotein Monooxygenases.

Six new angucycline structures, including spirocyclione A (), which contains an unusual oxaspiro[5.5]undecane architecture, and its ring-A-cleaved product spirocyclione B (), were discovered by heterologous expression of a type II polyketide biosynthetic gene cluster captured from a marine actinomycete strain sp. HDN155000.

Alginate oligosaccharides exert protective effects on hydrogen peroxide-induced senescence in H9C2 cardiomyocytes by regulating the redox state of cells.

Aging is a known independent risk factor for several cardiovascular diseases. Here, we evaluated potential effects and possible mechanisms through which alginate oligosaccharides (AOS) affect hydrogen peroxide (HO)-induced senescence in H9C2 cardiomyocytes. A series of AOS molecules, including oligoM, oligoG, M-5, and G-5, were investigated.

A β-1,3/1,6-glucan enhances anti-tumor effects of PD1 antibody by reprogramming tumor microenvironment.

Checkpoint blockades have emerged as a frontline approach in cancer management, designed to enhance the adaptive immune response against tumors. However, its clinical efficacy is limited to a narrow range of tumor types, which necessitates the exploration of novel strategies that target another main branch of the immune system. One such potential strategy is the therapeutic modulation of pattern recognition receptors (PRRs) pathways in innate immune cells, which have shown promise in tumor eradication.

Synergistic Anti-Tumor Efficacy Achieved by Reversing Drug Resistance through the Regulation of the Tumor Immune Microenvironment with IL-12 and Osimertinib Combination Therapy.

The objective of this study was to investigate the role of IL-12 in enhancing the anti-tumor efficacy of the small molecule targeted drug osimertinib in resistant tumor models and reversing resistance mechanisms. We utilized paired non-small cell lung cancer H1975 tumor tissues, establishing mouse tumor models with diverse tumor immune microenvironments. Analytical methods including immunohistochemistry and immunofluorescence were employed to compare immune cell infiltration, cytokines, effector molecules, and protein changes in resistant signaling pathways in tumor tissues, shedding light on IL-12's mechanism of action in enhancing osimertinib efficacy and reversing resistance.

Structural characterization of the glucan from Gastrodia elata Blume and its ameliorative effect on DSS-induced colitis in mice.

The polysaccharide glucan was extracted from Gastrodia elata Blume, and its structural characterizations and beneficial effects against acute dextran sulfate sodium (DSS)-induced ulcerative colitis were investigated. The results showed that a polysaccharide GP with a molecular weight of 811.0 kDa was isolated from G.

Development and Validation of a Liquid Chromatography-Tandem Mass Spectrometry Method for Screening Potential Citrate Lyase Inhibitors from a Library of Marine Compounds.

Tuberculosis, a persistent illness caused by , remains a significant global public health challenge. The widespread use of anti-tuberculosis drugs has resulted in the emergence of drug-resistant strains, which complicates treatment efforts. Addressing this issue is crucial and hinges on the development of new drugs that can effectively target the disease.

Psammaplin A analogues with modified disulfide bond targeting histone deacetylases: Synthesis and biological evaluation.

Psammaplin A (PsA), a symmetrical bromotyrosine-derived disulfide marine metabolite, has been reported could inhibit HDAC1/2/3 through its thiol monomer. Inspired by the disuflide bond structure of this marine natural product, we designed and synthesized a series of PsA analogues, in which the disulfide bond of PsA was replaced with diselenide bond or cyclic disulfide/diselenide/selenenylsulfide motifs. We also studied the HDAC inhibition, cell growth inhibition, and apoptosis induction of these PsA analogues.

Discovery, Total Synthesis, and Anti-Inflammatory Evaluation of Naturally Occurring Naphthopyrone-Macrolide Hybrids as Potent NLRP3 Inflammasome Inhibitors.

Numerous clinical disorders have been linked to the etiology of dysregulated NLRP3 (NACHT, LRR, and PYD domain-containing protein 3) inflammasome activation. Despite its potential as a pharmacological target, modulation of NLRP3 activity remains challenging. Only a sparse number of compounds have been reported that can modulate NLRP3 and none of them have been developed into a commercially available drug.

Targeting senescent HDF with the USP7 inhibitor P5091 to enhance DFU wound healing through the p53 pathway.

Objective: The objective of this study was to examine the potential of USP7 as a target for senolytic therapy and to investigate the molecular mechanism by which its inhibitor selectively induced apoptosis in senescent HDF and enhanced DFU wound healing.

Methods: Clinical samples of DFU were collected to detect the expression of USP7 and aging-related proteins using immunohistochemistry and Western blot. In addition, β-galactosidase staining, qPCR, flow cytometry, ROS and MMP kits, and Western blot were used to analyze the biological functions of P5091 on senescence, cycle, and apoptosis.

Design of Selective PARP-1 Inhibitors and Antitumor Studies.

Designing selective PARP-1 inhibitors has become a new strategy for anticancer drug development. By sequence comparison of PARP-1 and PARP-2, we identified a possible selective site (S site) consisting of several different amino acid residues of α-5 helix and D-loop. Targeting this S site, 140 compounds were designed, synthesized, and characterized for their anticancer activities and mechanisms.

Characterization of a novel circular bacteriocin from 1-3, and its mode of action against .

In this study, isolate 1-3 was selected out for its anti- Listeria potency, from which a novel circular bacteriocin, velezin, was purified out of the fermentate, and then characterized. Facilitated with a broad antibacterial spectrum, velezin has demonstrated decent inhibitive activity against of foodborne pathogen ATCC 19115. It exerted the antibacterial activity through damaging the membrane integrity of targeted cell and causing leakage of vital elements, including K ion.