Engineering allorejection-resistant CAR-NKT cells from hematopoietic stem cells for off-the-shelf cancer immunotherapy.

The clinical potential of current FDA-approved chimeric antigen receptor (CAR)-engineered T (CAR-T) cell therapy is encumbered by its autologous nature, which presents notable challenges related to manufacturing complexities, heightened costs, and limitations in patient selection. Therefore, there is a growing demand for off-the-shelf universal cell therapies. In this study, we have generated universal CAR-engineered NKT (CAR-NKT) cells by integrating iNKT TCR engineering and HLA gene editing on hematopoietic stem cells (HSCs), along with an ex vivo, feeder-free HSC differentiation culture.

Advancements in CRISPR screens for the development of cancer immunotherapy strategies.

CRISPR screen technology enables systematic and scalable interrogation of gene function by using the CRISPR-Cas9 system to perturb gene expression. In the field of cancer immunotherapy, this technology has empowered the discovery of genes, biomarkers, and pathways that regulate tumor development and progression, immune reactivity, and the effectiveness of immunotherapeutic interventions. By conducting large-scale genetic screens, researchers have successfully identified novel targets to impede tumor growth, enhance anti-tumor immune responses, and surmount immunosuppression within the tumor microenvironment (TME).

Comparison of three in-situ gels composed of different oil types.

A phospholipid-based phase separation in-situ gel (PPSG) system, which consists of phospholipids, medium chain oil (triglyceride) and ethanol as basic ingredients, has been previously developed in our lab. In addition, glycerol monooleate (monoglyceride) and glycerol dioleate (diglyceride) were also reported to be able to form liquid crystal gels. Monoglyceride, diglyceride and triglyceride have different degrees of hydroxyl substitution in glycerol and therefore different amphiphilic properties, which may cause different properties of gels composed of them.

Testosterone-induced benign prostatic hyperplasia rat and dog as facile models to assess drugs targeting lower urinary tract symptoms.

Benign prostatic hyperplasia (BPH) is an age-related disease, affecting a majority of elderly men worldwide. Medical management of BPH is an alternative to surgical treatment of this disease. Currently, α1-adrenergic receptor (α1-AR) antagonists are among the first line drugs to treat BPH by reducing the tension of urinary track and thus the obstructive symptoms in voiding.

Oxymatrine Sensitizes the HaCaT Cells to the IFN-γ Pathway and Downregulates MDC, ICAM-1, and SOCS1 by Activating p38, JNK, and Akt.

Decreased interferon (IFN)-γ levels and increased levels of macrophage-derived chemokine (MDC) and intercellular adhesion molecule (ICAM)-1 are known to be involved in allergic skin diseases, such as eczema and atopic dermatitis. Activation of the IFN-γ and its downstream interleukin-12 (IL-12) pathway can correct these diseases. Suppressor of cytokine signaling 1 (SOCS1) is a cytokine signaling inhibitor that blocks downstream pathways of IFN-γ by blocking the mitogen-activated protein kinase (MAPK) and protein kinase B (Akt) signaling pathways.

Design, Synthesis, and Biological Evaluation of Indoline and Indole Derivatives as Potent and Selective α1A-Adrenoceptor Antagonists.

A series of indoline and indole derivatives were designed, synthesized, and evaluated as selective α1A-adrenergic receptor (α1A-AR) antagonists for the treatment of benign prostatic hyperplasia (BPH). In this study, two highly selective and potent α1A-AR antagonists, compounds (R)-14r (IC50 = 2.7 nM, α1B/α1A = 640.