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).

Advancements and challenges in immunocytokines: A new arsenal against cancer.

Immunocytokines, employing targeted antibodies to concentrate cytokines at tumor sites, have shown potential advantages such as prolonged cytokine half-lives, mitigated adverse effects, and synergistic antitumor efficacy from both antibody and cytokine components. First, we present an in-depth analysis of the advancements of immunocytokines evaluated in preclinical and clinical applications. Notably, anti-PD-1-based immunocytokines can redirect cytokines to intratumoral CD8 T cells and reinvigorate them to elicit robust antitumor immune responses.

The role of the microbiota-gut-brain axis in methamphetamine-induced neurotoxicity: Disruption of microbial composition and short-chain fatty acid metabolism.

Methamphetamine (METH) abuse is associated with significant neurotoxicity, high addiction potential, and behavioral abnormalities. Recent studies have identified a connection between the gut microbiota and METH-induced neurotoxicity and behavioral disorders. However, the underlying causal mechanisms linking the gut microbiota to METH pathophysiology remain largely unexplored.

Nonalcoholic steatohepatitis increases plasma retention of sorafenib-glucuronide in a mouse model by altering hepatocyte hopping.

Hepatocyte hopping is the hepatocyte-to-sinusoid-to-hepatocyte shuttling that increases the efficiency of hepatic elimination of xenobiotics. This phenomenon is mediated efflux of hepatic metabolites by Mrp3 and reuptake by Oatp transporters in sequential hepatocytes until eventual biliary efflux by Mrp2. Sorafenib-glucuronide (SFB-G), the major metabolite of sorafenib (SFB), undergoes hepatocyte hopping, leading to efficient biliary elimination.

Exemplifying interspecies variation of liposome fate by the effects of anti-PEG antibodies.

The different fate of liposomes among species has been discovered and mentioned in many studies, but the underlying mechanisms have not been explored. In the present work, we concentrated on the fate of PEGylated liposomes (sLip) in three commonly used species (mice, rats, and dogs). It was exhibited that the accelerated blood clearance (ABC) phenomenon and hypersensitivity in large animals (beagle dogs) were much more significant than that in rodents.

Spatiotemporally responsive cascade bilayer microneedles integrating local glucose depletion and sustained nitric oxide release for accelerated diabetic wound healing.

High glucose level, bacterial infection, and persistent inflammation within the microenvironment are key factors contributing to the delay of diabetic ulcers healing, while traditional therapeutic methods generally fail to address these issues simultaneously. Here, we present a spatiotemporally responsive cascade bilayer microneedle (MN) patch for accelerating diabetic wound healing local glucose depletion and sustained nitric oxide (NO) release for long-term antibacterial and anti-inflammatory effects. The MN patch (G/AZ-MNs) possesses a degradable tip layer loading glucose oxidase (GOx), as well as a dissolvable base layer encapsulating l-arginine (Arg)-loaded nanoparticles (NPs).

Erratum: Author correction to "Identification of anthelmintic parbendazole as a therapeutic molecule for HNSCC through connectivity map-based drug repositioning" [Acta Pharm Sin B 12 (2022) 2429-2442].

[This corrects the article DOI: 10.1016/j.apsb.

Immunometabolic rewiring in macrophages for periodontitis treatment nanoquercetin-mediated leverage of glycolysis and OXPHOS.

Periodontitis is a chronic inflammatory disease marked by a dysregulated immune microenvironment, posing formidable challenges for effective treatment. The disease is characterized by an altered glucose metabolism in macrophages, specifically an increase in aerobic glycolysis, which is linked to heightened inflammatory responses. This suggests that targeting macrophage metabolism could offer a new therapeutic avenue.

Adipose ADM2 ameliorates NAFLD promotion of ceramide catabolism.

The adipose tissue of mammals represents an important energy-storing and endocrine organ, and its dysfunction is relevant to the onset of several health problems, including non-alcoholic fatty liver disease (NAFLD). However, whether treatments targeting adipose dysfunction could alleviate NAFLD has not been well-studied. Adrenomedullin 2 (ADM2), belonging to the CGRP superfamily, is a protective peptide that has been shown to inhibit adipose dysfunction.

Targeting toll-like receptor 7 as a therapeutic development strategy for systemic lupus erythematosus.

Endosomal TLRs (TLR3/7/8/9) are highly analogous innate immunity sensors for various viral or bacterial RNA/DNA molecular patterns. Among them, TLR7, in particular, has been suggested to be a target for various inflammatory disorders and autoimmune diseases including systemic lupus erythematosus (SLE); but few small-molecule inhibitors with elaborated mechanism have been reported in literature. Here, we reported a well-characterized human TLR7-specific small-molecule inhibitor, TH-407b, with promising potency and negligible cytotoxicity through a novel binding mechanism.

Next-generation aluminum adjuvants: Immunomodulatory layered double hydroxide NanoAlum reengineered from first-line drugs.

Aluminum adjuvants (Alum), approved by the US Food and Drug Administration, have been extensively used in vaccines containing recombinant antigens, subunits of pathogens, or toxins for almost a century. While Alums typically elicit strong humoral immune responses, their ability to induce cellular and mucosal immunity is limited. As an alternative, layered double hydroxide (LDH), a widely used antacid, has emerged as a novel class of potent nano-aluminum adjuvants (NanoAlum), demonstrating advantageous physicochemical properties, biocompatibility and adjuvanticity in both humoral and cellular immune responses.

Erratum to "Phenylalanine deprivation inhibits multiple myeloma progression by perturbing endoplasmic reticulum homeostasis" [Acta Pharm Sin B 14 (2024) 3493-3512].

[This corrects the article DOI: 10.1016/j.apsb.

Solubilization techniques used for poorly water-soluble drugs.

About 40% of approved drugs and nearly 90% of drug candidates are poorly water-soluble drugs. Low solubility reduces the drugability. Effectively improving the solubility and bioavailability of poorly water-soluble drugs is a critical issue that needs to be urgently addressed in drug development and application.

Precise targeting of lipid metabolism in the era of immuno-oncology and the latest advances in nano-based drug delivery systems for cancer therapy.

Over the past decade, research has increasingly identified unique dysregulations in lipid metabolism within the tumor microenvironment (TME). Lipids, diverse biomolecules, not only constitute biological membranes but also function as signaling molecules and energy sources. Enhanced synthesis or uptake of lipids in the TME significantly promotes tumorigenesis and proliferation.

Nanomedicine regulating PSC-mediated intercellular crosstalk: Mechanisms and therapeutic strategies.

Pancreatic fibrosis (PF) is primarily distinguished by the stimulation of pancreatic stellate cells (PSCs) and excessive extracellular matrix deposition, which is the main barrier impeding drug delivery and distribution. Recently, nanomedicine, with efficient, targeted, and controllable drug release characteristics, has demonstrated enormous advantages in the regression of pancreas fibrotic diseases. Notably, paracrine signals from parenchymal and immune cells such as pancreatic acinar cells, islet cells, pancreatic cancer cells, and immune cells can directly or indirectly modulate PSC differentiation and activation.

Colon-specific controlled release of oral liposomes for enhanced chemo-immunotherapy against colorectal cancer.

A colon-specific drug delivery system has great potential for the oral administration of colorectal cancer. However, the uncontrollable fate of liposomes makes their effectiveness for colonic location, and intratumoral accumulation remains unsatisfactory. Here, an oral colon-specific drug delivery system (CBS-CS@Lipo/Oxp/MTZ) was constructed by covalently conjugating spores (CBS) with drugs loaded chitosan (CS)-coated liposomes, where the model chemotherapy drug oxaliplatin (Oxp) and anti-anaerobic bacteria agent metronidazole (MTZ) were loaded.

Multiepitope recognition technology promotes the in-depth analysis of antibody‒drug conjugates.

The dynamic tracking of antibody‒drug conjugates (ADCs) in serum is crucial. However, a versatile bioanalytical platform is lacking due to serious matrix interferences, the heterogeneity and complex biotransformation of ADCs, and the recognition deficiencies of traditional affinity technologies. To overcome this, a multiepitope recognition technology (MERT) was developed by simultaneously immobilizing CDR and non-CDR ligands onto MOF@AuNPs.

An overview of the functions and mechanisms of APOBEC3A in tumorigenesis.

The APOBEC3 (A3) family plays a pivotal role in the immune system by performing DNA/RNA single-strand deamination. Cancers mostly arise from the accumulation of chronic mutations in somatic cells, and recent research has highlighted the A3 family as a major contributor to tumor-associated mutations, with A3A being a key driver gene leading to cancer-related mutations. A3A helps to defend the host against virus-induced tumors by editing the genome of cancer-associated viruses that invade the host.

Novel benzothiazole derivatives target the Gac/Rsm two-component system as antibacterial synergists against infections.

The management of antibiotic-resistant, bacterial biofilm infections in skin wounds poses an increasingly challenging clinical scenario. infection is difficult to eradicate because of biofilm formation and antibiotic resistance. In this study, we identified a new benzothiazole derivative compound, (IC = 43.