Type A cholesterol-dependent cytolysins translocate to the trans-Golgi network for NLRP3 inflammasome activation.

Cholesterol-dependent cytolysins (CDCs) constitute the largest group of pore-forming toxins and serve as critical virulence factors for diverse pathogenic bacteria. Several CDCs are known to activate the NLRP3 inflammasome, although the mechanisms are unclear. Here we discovered that multiple CDCs, which we referred to as type A CDCs, were internalized and translocated to the trans-Golgi network (TGN) to remodel it into a platform for NLRP3 activation through a unique peeling membrane mechanism.

Suppression of deficiency-induced cellular senescence and interferonopathies by inhibition of DNA damage response.

TREX1 encodes a major DNA exonuclease and mutations of this gene are associated with type I interferonopathies in human. Mice with deletion or mutation have shortened life spans accompanied by a senescence-associated secretory phenotype. However, the contribution of cellular senescence in deficiency-induced type I interferonopathies remains unknown.

The initiation of oxidative stress and therapeutic strategies in wound healing.

When the production of reactive oxygen species (ROS) is overloaded surpassing the capacity of the reductive rheostat, mammalian cells undergo a series of oxidative damage termed oxidative stress (OS). This phenomenon is ubiquitously detected in many human pathological conditions. Wound healing program implicates continuous neovascularization, cell proliferation, and wound remodeling.

Engineered Magnetic Polymer Nanoparticles Can Ameliorate Breast Cancer Treatment Inducing Pyroptosis-Starvation along with Chemotherapy.

Nanotechnology has shown a revolution in cancer treatments, including breast cancers. However, there remain some challenges and translational hurdles. Surgery, radiotherapy, and chemotherapy are the primary treatment methods for breast cancer, although drug combinations showed promising results in preclinical studies.

Celastrol ameliorates autoimmune disorders in Trex1-deficient mice.

Celastrol is one of most potent bioactive molecule isolated from the medicinal plant Tripterygium wilfordii (Thunder God Vine) and is well known for its potential therapeutic value against various chronic diseases including the autoimmune diseases, such as systemic lupus erythematosus and Aicardi-Goutieres syndrome, or other interferonopathies. However, the underlying mechanism of celastrol function remains unclear. Here we showed that celastrol caused inhibition of interferon regulatory factor 3 (IRF3) activation leading to the down-regulation of the interferon response triggered by cytosolic nucleic acids in vitro and in vivo.

PNCK depletion inhibits proliferation and induces apoptosis of human nasopharyngeal carcinoma cells and .

Recent studies indicate that pregnancy upregulated non-ubiquitous calmodulin kinase (PNCK) is significantly up-regulated in breast and renal carcinomas. However, the expression profile and its biological relevance of PNCK in nasopharyngeal carcinoma (NPC) have not been elucidated. The expression level of PNCK was detected in specimens of NPC (n=10) and normal tissues (n=10) by real-time PCR and immunohistochemistry.

cGAS activation causes lupus-like autoimmune disorders in a TREX1 mutant mouse model.

TREX1 encodes a major cellular DNA exonuclease. Mutations of this gene in human cause cellular accumulation of DNA that triggers autoimmune diseases including Aicardi-Goutieres Syndrome (AGS) and systemic lupus erythematosus (SLE). We created a lupus mouse model by engineering a D18 N mutation in the Trex1 gene which inactivates the enzyme and has been found in human patients with lupus-like disorders.

Early discrimination of nasopharyngeal carcinoma based on tissue deoxyribose nucleic acid surface-enhanced Raman spectroscopy analysis.

Surface-enhanced Raman spectroscopy (SERS) was employed to detect deoxyribose nucleic acid (DNA) variations associated with the development of nasopharyngeal carcinoma (NPC). Significant SERS spectral differences between the DNA extracted from early NPC, advanced NPC, and normal nasopharyngeal tissue specimens were observed at 678, 729, 788, 1337, 1421, 1506, and 1573??cm?1, which reflects the genetic variations in NPC. Principal component analysis combined with discriminant function analysis for early NPC discrimination yielded a diagnostic accuracy of 86.

[Regulation and evasion of host immune responses by Epstein-Barr virus].

Epstein-Barr virus (EBV) is the first identified human oncogenic DNA virus in the gamma-herpesvirus family. EBV triggers a cascade events of innate immune responses through Toll-like receptor signaling including the production of type I interferons and the activation of functional autophagy. However, EBV has developed much more elaborate and sophisticated strategies for subverting and escaping the host immune system, such as limiting its own gene expression, activing the host ubiquitin-specific protease system, and interfering ubiquitin modification.