Peptide-Scaffolded Detergents for Membrane Protein Studies.

Detergents are essential for preserving the structural integrity and functionality of membrane proteins (MPs) outside the biological membrane or in aqueous solution, and thus ensuring accurate biochemical and structural analyses. Here, we introduce peptide-scaffolded detergents, a novel class of hybrid molecules formed by preassembling detergent monomers with peptides of varying lengths, mediated via Click chemistry. These detergents are characterized by scalable, straightforward synthesis and enhanced solubility.

Berberine Derivative B68 Promotes Tumor Immune Clearance by Dual-Targeting BMI1 for Senescence Induction and CSN5 for PD-L1 Degradation.

Promoting tumor cell senescence arrests the cell cycle of tumor cells and activates the immune system to eliminate these senescent cells, thereby suppressing tumor growth. Nevertheless, PD-L1 positive senescent tumor cells resist immune clearance and possess the ability to secret various cytokines and inflammatory factors that stimulate the growth of tumor cells. Consequently, drugs capable of both triggering senescence in tumor cells and concurrently diminishing the expression of PD-L1 to counteract immune evasion are urgently needed.

A phosphoglycerate mutase 1 allosteric inhibitor restrains TAM-mediated colon cancer progression.

Colorectal cancer (CRC) is a prevalent malignant tumor often leading to liver metastasis and mortality. Despite some success with PD-1/PD-L1 immunotherapy, the response rate for colon cancer patients remains relatively low. This is closely related to the immunosuppressive tumor microenvironment mediated by tumor-associated macrophages (TAMs).

Exploring bifunctional molecules for anti-SARS-CoV-2 and anti-inflammatory activity through structure-based virtual screening, SAR investigation, and biological evaluation.

As new variants of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) continue to emerge, they raise increasing concerns about the efficacy of neutralizing antibodies and vaccines. This situation underscores the urgent need for specific drugs against the coronavirus disease 2019 (COVID-19). Given that COVID-19 is particularly associated with substantial inflammation, the development of novel, effective antiviral and anti-inflammatory agents represents a promising research direction.

Danggui Liuhuang Decoction ameliorates endothelial dysfunction by inhibiting the JAK2/STAT3 mediated inflammation.

Ethnopharmacological Relevance: Vascular endothelial dysfunction (VED) is recognized as a key triggering diabetic vascular complications. Danggui Liuhuang Decoction (DGLHD) has shown potential in mitigating these complications. However, the clinical efficacy of DGLHD in enhancing endothelial function, as well as the molecular mechanisms underlying its alleviation of Type 2 Diabetes-Related Vascular Endothelial Dysfunction (T2DM-VED), remains insufficiently understood.

Curcumin targets CXCL16-mediated podocyte injury and lipid accumulation in diabetic kidney disease treatment.

Among the complications of diabetes, diabetic kidney disease (DKD) frequently emerges, typified by the detrimental effects on renal function, manifesting through inflammation, dysregulated lipid metabolism, and harm to podocytes. Existing research underscores the significance of the soluble form of C-X-C chemokine ligand 16 (CXCL16) within the context of renal impairments. However, whether CXCL16 is involved in the pathogenesis of DKD remains elusive.

Utilizing DNA Logic Device for Precise Detection of Circulating Tumor Cells via High Catalytic Activity Au Nanoparticle Anchoring.

As medical advancements turn most cancers into manageable chronic diseases, new challenges arise in cancer recurrence monitoring. Detecting circulating tumor cells (CTCs) is crucial for monitoring cancer recurrence, but the current methods are cumbersome and costly. This study developed a new CTC detection system combining DNA aptamer recognition, hybridization chain reaction (HCR) technology, and DNA logic devices, enabling the one-step recognition of CTCs by identifying multiple membrane proteins.

Discovery of Chalcone Derivatives as Bifunctional Molecules with Anti-SARS-CoV-2 and Anti-inflammatory Activities.

Danshensu extracted with traditional Chinese medicine has a wide range of bioactivities. Danshensu containing a catechol moiety has a moderate inhibitory effect on SARS-CoV-2 3CL (IC = 2.2 μM) by a reversible covalent interaction and exhibits good anti-inflammatory activity.

Demethylzeylasteral induces PD-L1 ubiquitin-proteasome degradation and promotes antitumor immunity targeting USP22.

Programmed cell death ligand-1 (PD-L1) is a T cell inhibitory immune checkpoint molecule that interacts with programmed cell death-1 (PD-1) to promote immune escape of tumor cells. Compared with antibody therapies, small molecule drugs show better prospects due to their advantages such as higher bioavailability, better tissue penetration, and reduced risk of immunogenicity. Here, we found that the small molecule demethylzeylasteral (Dem) can significantly downregulate the expression of PD-L1 in colorectal cancer cells and enhance the killing effect of T cells on tumor cells.

Development of Glycosylation Protocols Using Glycosyl -Phenylethynyl Pyrrole-2-carboxylates as Donors.

We herein introduce glycosyl -phenylethynyl pyrrole-2-carboxylates (PEPCs) as novel and highly efficient glycosyl donors. The unique inclusion of the pyrrole group, serving as both an electron-donating group and an -tethering scaffold, imparts exceptional shelf stability while retaining reactivity for glycosylation reactions. PEPC donors exhibit broad utility for both - and -glycosylation across a variety of substrates.

The involvement and possible targeting of cardiolipins degradation and disturbed linoleic acid metabolism in cardiac atrophy under cancer cachexia.

Cardiac atrophy is one of the critical characteristics of cancer cachexia though its mechanisms had not been fully clarified. In the present study, to study the mechanisms of cardiac atrophy in cancer cachexia and search for possible drug targets, cancer cachexia mice bearing C26 colon tumor cells and cultured H9c2 cardiomyocytes induced with simulated cancer cachexia injuries were used as in vivo and in vitro model, respectively. Results of both spatial metabolomics and LC-MS non-targeted metabolomics analysis of heart tissues suggested the disturbance of glycerophospholipid and fatty acid metabolism in the cancer cachexia hearts.

Network Medicine-Based Strategy Identifies Maprotiline as a Repurposable Drug by Inhibiting PD-L1 Expression via Targeting SPOP in Cancer.

Immune checkpoint inhibitors (ICIs) are drugs that inhibit immune checkpoint (ICP) molecules to restore the antitumor activity of immune cells and eliminate tumor cells. Due to the limitations and certain side effects of current ICIs, such as programmed death protein-1, programmed cell death-ligand 1, and cytotoxic T lymphocyte-associated antigen 4 (CTLA4) antibodies, there is an urgent need to find new drugs with ICP inhibitory effects. In this study, a network-based computational framework called multi-network algorithm-driven drug repositioning targeting ICP (Mnet-DRI) is developed to accurately repurpose novel ICIs from ≈3000 Food and Drug Administration-approved or investigational drugs.

The Activation of Muscarinic Acetylcholine Receptors Protects against Neuroinflammation in a Mouse Model through Attenuating Microglial Inflammation.

Neuroinflammation is a critical factor that contributes to neurological impairment and is closely associated with the onset and progression of neurodegenerative diseases. In the central nervous system (CNS), microglia play a pivotal role in the regulation of inflammation through various signaling pathways. Therefore, mitigating microglial inflammation is considered a promising strategy for restraining neuroinflammation.

Discovery of Tetrahydro Tanshinone I as a Naturally Occurring Covalent -Inhibitor Against Gut Microbial Bile Salt Hydrolases.

Gut microbial bile salt hydrolases (gmBSHs), an important class of bacteria-produced cysteine hydrolases, play a crucial role in bile acid metabolism. Modulating the total gmBSH activity is a feasible way for ameliorating some metabolic diseases including colorectal cancer, type 2 diabetes, and obesity. This study reported the discovery and characterization of a botanical compound as a covalent -inhibitor of gmBSHs.

Interferon-I modulation and natural products: Unraveling mechanisms and therapeutic potential in severe COVID-19.

The coronavirus disease 2019 (COVID-19) pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) continues to pose a significant global public health threat, particularly to older adults, pregnant women, and individuals with underlying chronic conditions. Dysregulated immune responses to SARS-CoV-2 infection are believed to contribute to the progression of COVID-19 in severe cases. Previous studies indicates that a deficiency in type I interferon (IFN-I) immunity accounts for approximately 15 %-20 % of patients with severe pneumonia caused by COVID-19, highlighting the potential therapeutic importance of modulating IFN-I signals.

An activity-based sensing fluorogenic probe for monitoring O-methyltransferase in plants.

Activity-based sensing probes are powerful tools for monitoring enzymatic activities in complex biological samples such as cellular and live animals; however, their application in plants remains challenging. Herein, fourteen activity-based fluorescent probes were assayed against Arabidopsis O-methyltransferases (AtOMTs). One probe, 3-BTD, displayed a high selectivity, reactivity, and fluorescence response toward AtOMTs especially the isoform AtCCoAOMT.

Investigating the mechanism of ferroptosis induction by sappanone A in hepatocellular carcinoma: NRF2/xCT/GPX4 axis.

Hepatocellular carcinoma (HCC) is a prevalent and lethal malignancy with significant global impact, necessitating the development of novel therapeutic strategies and drugs. Ferroptosis, a newly identified form of iron-dependent programmed cell death, has emerged as a promising strategy to combat HCC. Sappanone A, an isoflavone compound derived from the heartwood of Biancaea sappan (L.

Total astragalus saponins attenuate primary sclerosing cholangitis in mice by upregulation of TGR5.

Total astragalus saponins (TAS) are the main active components of astragali radix, and have potent anti-hepatic fibrosis effect. However, the therapeutic efficacy of TAS and their potential mechanisms in the treatment of primary sclerosing cholangitis (PSC) remain unclear. In this study, two mouse models of PSC, including 3,5-Diethoxycarbonyl-1,4-Dihydro-2,4,6-Collidine (DDC)-induced PSC and Mdr2 spontaneous PSC, and the Tgr5 mice were used to investigate the therapeutic effect and mechanisms of TAS.