Injectable bioresponsive bone adhesive hydrogels inhibit NLRP3 inflammasome on demand to accelerate diabetic fracture healing.

Diabetes is associated with excessive inflammation, which negatively impacts the fracture healing process and delays bone repair. Previously, growing evidence indicated that activation of the nod-like receptor (NLR) family, such as nod-like receptor thermal protein domain-associated protein 3 (NLRP3) inflammasome induces a vicious cycle of chronic low-grade inflammatory responses in diabetic fracture. Here, we describe the synthesis of a bone adhesive hydrogel that can be locally injected into the fracture site and releases a natural inhibitor of NLRP3 (rutin) in response to pathological cue reactive oxygen species activity (ROS).

Generalized pustular psoriasis: immunological mechanisms, genetics, and emerging therapeutics.

Generalized pustular psoriasis (GPP) is a rare human autoinflammatory disorder with life-threatening systemic effects. Keratinocyte-derived interleukin (IL)-36 signaling has been identified as a key mediator of immune response in the skin of affected individuals. Recognition of various mutations along the IL-36 axis and the downstream nuclear transcription factor κB (NF-κB) signaling have established GPP as genetically, immunologically, and histopathologically distinct and amenable to immunomodulation, which is epitomized by the recent success of IL-36 antagonism.

Direct engulfment of synapses by overactivated microglia due to cadmium exposure and the protective role of Nrf2.

Cadmium (Cd), a notorious environmental pollutant, has been linked to neurological disorders, but the underlying mechanism remains elusive. We aimed to explore the role of microglia in Cd-induced synaptic damages at environmentally relevant doses and whether microglia directly engulf synaptic structures. Nrf2 is deeply implicated in the status of microglial activation; therefore, we also investigated whether it is involved in the above process.

Psychometric evaluation of the elderly mobility scale in Indonesia.

Background: The Elderly Mobility Scale (EMS) is widely used to identify mobility limitations in older adults, though it has not been validated in Indonesia.

Aim: To evaluate the reliability and validity of the Indonesian version of the EMS (EMS-I).

Method: A cross-sectional design involving 230 older adults in South Tangerang City, Indonesia, was used.

Targeting autophagy plus high-dose CDK4/6 inhibitors in advanced HR+HER2- breast cancer: A phase 1b/2 trial.

Background: The unmet needs of managing patients with hormone receptor-positive/human epidermal growth factor receptor 2-negative (HR+/HER2-) breast cancer who progress after cyclin-dependent kinase (CDK)4/6 inhibitor (CDK4/6i) treatment remain unclarified.

Methods: This was a phase 1b/2, single-arm, open-label study that enrolled 29 patients with HR+/HER2- breast cancer who experienced first-line palbociclib treatment failure. The primary endpoint was the incidence of dose-limiting toxicity (DLT).