Glioblastoma multiforme (GBM) remains incurable despite aggressive implementation of multimodal treatments after surgical debulking. Almost all patients with GBM relapse within a narrow margin around the initial resected lesion due to postsurgery residual glioma stem cells (GSCs). Tracking and eradicating postsurgery residual GSCs is critical for preventing postoperative relapse of this devastating disease, yet effective strategies remain elusive. Here, we report a cavity-injectable nanoporter-hydrogel superstructure that creates GSC-specific chimeric antigen receptor (CAR) macrophages/microglia (MΦs) surrounding the cavity to prevent GBM relapse. Specifically, we demonstrate that the CAR gene–laden nanoporter in the hydrogel can introduce GSC-targeted CAR genes into MΦ nuclei after intracavity delivery to generate CAR-MΦs in mouse models of GBM. These CAR-MΦs were able to seek and engulf GSCs and clear residual GSCs by stimulating an adaptive antitumor immune response in the tumor microenvironment and prevented postoperative glioma relapse by inducing long-term antitumor immunity in mice. In an orthotopic patient–derived glioblastoma humanized mouse model, the combined treatment with nanoporter-hydrogel superstructure and CD47 antibody increased the frequency of positive immune responding cells and suppressed the negative immune regulating cells, conferring a robust tumoricidal immunity surrounding the postsurgical cavity and inhibiting postoperative glioblastoma relapse. Therefore, our work establishes a locoregional treatment strategy for priming cancer stem cell–specific tumoricidal immunity with broad application in patients suffering from recurrent malignancies.

Cyclooxygenase (COX) and Lipoxygenase (LOX) are essential enzymes for arachidonic acid (AA) to eicosanoids conversion. These AA-derived eicosanoids are essential for initiating immunological responses, causing inflammation, and resolving inflammation. Dual COX/5-LOX inhibitors are believed to be promising novel anti-inflammatory agents. They inhibit the synthesis of prostaglandins (PGs) and leukotrienes (LTs), but have no effect on lipoxin formation. This mechanism of combined inhibition circumvents certain limitations for selective COX-2 inhibitors and spares the gastrointestinal mucosa. Natural products, i.e. spice chemicals and herbs, offer an excellent opportunity for drug discovery. They have proven anti-inflammatory properties. However, the potential of a molecule to be a lead/ drug candidate can be much more enhanced if it has the property of inhibition in a dual mechanism. Synergistic activity is always a better option than the molecule's normal biological activity. Herein, we have explored the dual COX/5-LOX inhibition property of the three major potent phytoconsituents (curcumin, capsaicin, and gingerol) from Indian spices using in silico tools and biophysical techniques in a quest to identify their probable inhibitory role as anti-inflammatory agents. Results revealed the dual COX/5-LOX inhibitory potential of curcumin. Gingerol and capsaicin also revealed favorable results as dual COX/5-LOX inhibitors. Our results are substantiated by target similarity studies, molecular docking, molecular dynamics, energy calculations, DFT, and QSAR studies. In experimental inhibitory (in vitro) studies, curcumin exhibited the best dual inhibitory activities against COX-1/2 and 5-LOX enzymes. Capsaicin and gingerol also showed inhibitory potential against both COX and LOX enzymes. In view of the anti-inflammatory potential these spice chemicals, this research could pave the way for more scientific exploration in this area for drug discovery.

The nomadic pastoral indigenous communities of the Ladakhi people share roots with Tibetan culture in terms of food, clothing, religion, festivals, and habits, and rely widely on plant resources for survival and livelihood. This survey was conducted during 2019–2021 to document the indigenous knowledge about plant resources of the Balti, Beda, and Brokpa communities of the Ladakh region, trans-Himalayas. Open- and close-ended semi-structured interviews (N = 184) and group discussions (N = 17) were used to collect the data. Quantitative data was further analyzed using various statistical tools. A total of 105 plant species belonging to 82 genera and 39 families were used as medicine, fuel wood, fragrance, oil, food, flavor, fodder, decoration, and dye. Among these, medicinal use was most prevalent, with 70% of use reports, followed by fodder and fuel wood. Leaves (27%) were the most preferred plant part used, followed by roots and flowers. The principal component analysis revealed five clusters of ethnobotanical usage, i.e., food, medicine, fuel wood, fodder, and fragrance, oil, dye, and flavor. The maximum number of plant species used was reported by the Brokpa, while the Beda reported the minimum number of plant species uses. Delphinium brunonianum, Waldheimia tomentosa, and Juniperus indica played a significant role in the cultural and religious ritual aspects, whereas Allium przewalskianum, Waldheimia tomentosa, Juniperus indica, and Hippophae rhamnoides were commonly used as a livelihood source among Ladakhi communities. The local people collected most plants (65%) for self-consumption, while the rest (35%) were sold in markets as a source of income. The sustainable utilization and management of plant resources by local people is a strategy to boost livelihoods and food security and alleviate poverty.