Kombucha tea is a traditional beverage originating from China and has recently gained popularity worldwide. Kombucha tea is produced by the fermentation of tea leaves and is characterized by its beneficial properties and varied chemical content produced during the fermentation process, which includes organic acids, amino acids, vitamins, minerals, and other biologically active compounds. Kombucha tea is often consumed as a health drink to combat obesity and inflammation; however, the bioactive effects of kombucha tea have not been thoroughly researched. In this study, we reveal the underlying mechanisms of the beneficial properties of kombucha tea and how they protect against obesity and inflammation by studying Drosophila models. We established an inflammatory Drosophila model by knocking down the lipid storage droplet-1 gene, a human perilipin-1 ortholog. In this model, dysfunction of lipid storage droplet-1 induces inflammation by enhancing the infiltration of hemocytes into adipose tissues, increasing reactive oxygen species production, elevating levels of proinflammatory cytokines, and promoting the differentiation of hemocytes into macrophages. These processes are regulated by the c-Jun N-terminal Kinase (JNK) pathway. Using this unique Drosophila model that mimics mammalian inflammation, we verified the beneficial effects of kombucha tea on reducing tissue inflammation. Our data confirms that kombucha tea effectively improves inflammatory conditions by suppressing the expression of cytokines and proinflammatory responses induced by lipid storage droplet-1 dysfunction. It was found that kombucha tea consumption alleviated the production of reactive oxygen species and activated the JNK signaling pathway, signifying its potential as an anti-inflammatory agent against systemic inflammatory responses connected to the JNK pathway. Kombucha tea reduced triglyceride accumulation by increasing the activity of Brummer (a lipase), thereby promoting lipolysis in third-instar larvae. Therefore, kombucha tea could be developed as a novel, functional beverage to protect against obesity and inflammation. Our study also highlights the potential use of this innovative model to evaluate the effects of bioactive compounds derived from natural products.

Autism spectrum disorder (ASD) is a multifaced neurodevelopmental disorder with considerable heterogeneity, in which over-generated reactive oxygen species (ROS) induce a cascade of pathological changes, including cellular apoptosis and inflammatory responses. Given the complex etiology of ASD, no effective treatment is available for ASD. In this work, a specific catalytic nanoenzyme, calcium hexacyanoferrate (III) nanocatalysts (CaH NCs), is designed and engineered for efficient ASD treatment. CaH NCs can mimic the activities of natural enzymes including superoxide dismutase, peroxidase, catalase, and glutathione peroxidase, which mitigates intracellular excessive ROS and regulates redox equilibrium. These CaH NCs modulate mitochondrial membrane potential, elevate B-cell lymphoma-2 levels, and suppress pro-apoptotic proteins, including Caspase-3 and B-cell lymphoma-2-associated X, thus effectively reducing cellular apoptosis. Importantly, CaH NCs alleviate inflammation by upregulating anti-inflammatory cytokine interleukin-10 and downregulating pro-inflammatory factors, resulting in attenuated activation of microglial and astrocytic and subsequent reduction in neuroinflammation. Subsequently, CaH NCs enhance social abilities, decrease anxiety levels, ameliorate repetitive behaviors, and improve learning and memory in ASD animal models through inflammation regulation and apoptosis inhibition. The CaH NCs in managing and preventing ASD represents a paradigm shift in autism treatment, paving the alternative but efficient way for clinical interventions in neurological conditions.

Small-interfering RNAs (siRNAs) offer promising prospects for treating pyroptosis-related autoimmune diseases. However, poor stability and off-target effects during in vivo transportation hinder their practical clinical applications. Precision delivery and adaptive release of siRNAs into inflamed tissues and immune cells could unleash their full therapeutic potential. This study establishes a pyroptotic-spatiotemporally selective siRNA delivery system (PMRC@siGSDME) that selectively targets inflammatory tissues, responds to pyroptosis, and exhibits remarkable therapeutic efficacy against various autoimmune diseases. Novel hybrid nanovesicles (NVs) are designed as a combination of pyroptotic macrophage membranes (PMs) and R8-cardiolipin-containing nanovesicles (RC-NVs). Evidence provides that PM-derived proteins involved in cell-cell interactions and membrane trafficking may contribute to the specificity of NVs to inflammatory tissue. In addition, cardiolipin anchored in the hybrid NVs increases its affinity for activated gasdermin E (GSDME) and achieves pyroptosis-adaptive release of siGSDME for the spatiotemporally selective suppression of immune responses. More importantly, PMRC@siGSDME displays significant anti-inflammatory and therapeutic effects in multiple mouse autoimmune disease models, including arthritis and inflammatory bowel disease (IBD). Collectively, an innovative siRNA delivery strategy precisely tailored for pyroptotic cells has been developed, paving the way for new treatments for autoimmune inflammatory diseases with minimal side effects and wide clinical applicability.

BACKGROUND: Angong Niuhuang Wan (AGNHW, ), is a classical medicinal formula in Traditional Chinese Medicine (TCM) that has been appreciated for its neuroprotective properties in ischemic cerebral injuries, yet its intricate mechanisms remain only partially elucidated.
OBJECTIVE: This study leverages advanced Mass cytometry (CyTOF) to analyze AGNHW\'s multifaceted immunomodulation effects in-depth, emphasizing previously underexplored areas.
RESULTS: AGNHW mitigated monocyte-derived macrophages (MoDM) infiltration in the brain, distinguishing its effects on those from microglia. While the vehicle group exhibited elevated inflammatory markers like CD4, CD8a, and CD44 in ischemic brains, the AGNHW-treated group attenuated their expressions, indicating AGNHW\'s potential to temper the post-ischemic inflammatory response. Systemically, AGNHW modulated fundamental immune cell dynamics, notably augmenting CD8+ T cells, B cells, monocytes, and neutrophil counts in the peripheral blood under post-stroke conditions. Intracellularly, AGNHW exhibited its targeted modulation of the signaling pathways, revealing a remarked inhibition of key markers like IκBα, indicating potential suppression of inflammatory responses in ischemic brain injuries.
CONCLUSIONS: This study offers a comprehensive portrait of AGNHW\'s immunomodulation effects on ischemic stroke, illuminating its dual sites of action-both cerebral and systemic-and its nuanced modulation of cellular and molecular dynamics.

Diabetic wounds pose a persistent challenge due to their slow healing nature, primarily caused by bacterial infection and excessive reactive oxygen species (ROS)-induced inflammation. In this study, carbon dots with synergistic antibacterial and antioxidant properties, referred to as AA-CDs, are developed specifically for diabetic wound healing using a straightforward solvothermal method. By utilizing cost-effective precursors like citric acid and ascorbic acid, AA-CDs are engineered to possess tailored functions of photothermal sterilization and ROS scavenging. The resulting AA-CDs demonstrats broad-spectrum antibacterial activity, particularly against multidrug-resistant strains, along with efficient ROS scavenging both in solution and within cells. Additionally, AA-CDs exhibits a protective effect against oxidative stress-induced damage. Notably, with a high photothermal conversion efficiency (41.18%), AA-CDs displays heat-enhanced antioxidant performance, providing not only augmented ROS scavenging but also additional protection against oxidative stress, yielding a true \"1 + 1 > 2\" effect. To facilitate their use in vivo, AA-CDs are incorporated into a thermally responsive hydrogel, which exhibits evident anti-inflammatory properties by modulating inflammatory factors and significantly promots the healing of diabetic wounds. This study underscores the value of integrated platforms for diabetic wound healing and highlights the potential of versatile CDs as promising therapeutic agents in biomedical applications.

Pain caused by lumbar disc herniation (LDH) severely compromises patients\' quality of life. The combination of steroid and local anesthetics is routinely employed in clinics to alleviate LDH-induced pain. However, the approach only mediates transient efficacy and requires repeated and invasive lumbar epidural injections. Here a paravertebrally-injected multifunctional hydrogel that can efficiently co-load and controlled release glucocorticoid betamethasone and anesthetics ropivacaine for sustained anti-inflammation, reactive oxygen species (ROS)-removal and pain relief in LDH is presented. Betamethasone is conjugated to hyaluronic acid (HA) via ROS-responsive crosslinker to form amphiphilic polymer that self-assemble into particles with ropivacaine loaded into the core. Solution of drug-loaded particles and thermo-sensitive polymer rapidly forms therapeutic hydrogel in situ upon injection next to the herniated disc, thus avoiding invasive epidural injection. In a rat model of LDH, multifunctional hydrogel maintains the local drug concentration 72 times longer than free drugs and more effectively inhibits the expression of pro-inflammatory cytokines and pain-related molecules including cyclooxygenase-2 (COX-2) and prostaglandin E2 (PGE2). Therapeutic hydrogel suppresses the LDH-induced pain in rats for 12 days while the equivalent dose of free drugs is only effective for 3 days. This platform is also applicable to ameliorate pain caused by other spine-related diseases.

Collaboration between cancer treatment and inflammation management has emerged as an integral facet of comprehensive cancer care. Nevertheless, the development of interventions concurrently targeting both inflammation and cancer has encountered significant challenges stemming from various external factors. Herein, a bioactive agent synthesized by genetically engineering melanin-producing Bacillus thuringiensis (B. thuringiensis) bacteria, simultaneously achieves eco-friendly photothermal agent and efficient reactive oxygen/nitrogen species (RONS) scavenger benefits, perfectly tackling present toughies from inflammation to cancer therapies. The biologically derived melanin exhibits exceptional photothermal-conversion performance, facilitating potent photonic hyperthermia that effectively eradicates tumor cells and tissues, thereby impeding tumor growth. Additionally, the RONS-scavenging properties of melanin produced by B. thuringiensis bacteria contribute to inflammation reduction, augmenting the efficacy of photothermal tumor repression. This study presents a representative paradigm of genetic engineering in B. thuringiensis bacteria to produce functional agents tailored for diverse biomedical applications, encompassing inflammation and cancer therapy.

Osteoarthritis (OA) is a degenerative joint disease primarily affecting the elderly. It is characterized by the progressive decline of joint cartilage and alterations in the underlying bone. Several probiotic strains have exhibited immunomodulatory and anti-inflammatory properties. Here, we examined the functions of live and dead Clostridium butyricum GKB7 (GKB7-L and GKB7-D) in a preclinical anterior cruciate ligament transection (ACLT)-enhanced OA procedure. Oral administration of GKB7-L and GKB7-D ameliorated ACLT-induced bone pain as assessed by weight-bearing behavioral testing but did not affect body weight. Micro-computed tomography (CT) results showed that GKB7-L and GKB7-D diminished ACLT-induced bone destruction and loss. GKB7-L and GKB7-D-enriched therapies also reduced ACLT-induced production of the pro-inflammatory cytokines interleukin (IL)-1β and tumor necrosis factor (TNF)-α, as well as the chondrolytic factor matrix metalloproteinase (MMP)-3, leading to inhibition of aggrecan and collagen type II degradation and thereby blocking cartilage breakdown. We therefore suggest that oral supplementation with GKB7-L or GKB7-D can be beneficial in the prevention and treatment of OA.

The environmental factor aryl hydrocarbon receptor (AhR), a key protein connecting the external environmental signals (e.g., environmental endocrine disruptor TCDD) to internal cellular processes, is involved in the activation of peripheral macrophages and inflammatory response in human body. Thus, there is widespread interest in finding compounds to anti-inflammatory response in macrophages by targeting human AhR. Here, ensemble docking based-virtual screening was first used to screen a library (~200,000 compounds) against human AhR ligand binding domain (LBD) and 25 compounds were identified as potential inhibitors. Then, 9 out of the 25 ligands were found to down-regulate the mRNA expression of CYP1A1 (a downstream gene of AhR signaling) in AhR overexpressing macrophages. The most potent compound AE-411/41415610 was selected for further study and found to reduce both mRNA and protein expressions level of CYP1A1 in mouse peritoneal macrophage. Moreover, protein chip signal pathway analysis indicated that AE-411/41415610 play a role in regulating JAK-STAT and AKT-mTOR pathways. In sum, the discovered hits with novel scaffolds provided a starting point for future design of more effective AhR-targeted lead compounds to regulate CYP1A1 expression of inflammatory peritoneal macrophages.

The effective treatment of chronic wounds represents a critical global medical challenge demanding urgent attention. Persistent inflammation, driven by an excess of reactive oxygen radicals, sets in motion a detrimental cycle leading to chronic wounds and impeding the natural healing process. This study develops a sprayable wound dressing by covalently grafting amino fullerene to carboxymethylated curdlan (CMC-C). This novel dressing exhibits excellent biocompatibility, antioxidant, and reactive oxygen species scavenging properties. Furthermore, it demonstrates a targeted affinity for HEK-a cells, efficiently reducing the inflammatory response while promoting cell proliferation and migration in vitro. Moreover, the animal experiment investigations reveal that CMC-C significantly accelerates chronic wounds healing by regulating the inflammatory process, promoting collagen deposition, and improving vascularization. These results demonstrate the potential of the sprayable dressing (CMC-C) in curing the healing of chronic wounds through the modulation of the inflammatory microenvironment. Overall, the sprayable hydrogel dressing based on water-soluble derivative of fullerene and curdlan emerges as a potential approach for clinical applications in the treatment of chronic wounds.