Consecutive palmitoylation and phosphorylation orchestrates NLRP3 membrane trafficking and inflammasome activation.

NLRP3 inflammasome activation, essential for cytokine secretion and pyroptosis in response to diverse stimuli, is closely associated with various diseases. Upon stimulation, NLRP3 undergoes subcellular membrane trafficking and conformational rearrangements, preparing itself for inflammasome assembly at the microtubule-organizing center (MTOC). Here, we elucidate an orchestrated mechanism underlying these ordered processes using human and murine cells.

ROS-dependent S-palmitoylation activates cleaved and intact gasdermin D.

Gasdermin D (GSDMD) is the common effector for cytokine secretion and pyroptosis downstream of inflammasome activation and was previously shown to form large transmembrane pores after cleavage by inflammatory caspases to generate the GSDMD N-terminal domain (GSDMD-NT). Here we report that GSDMD Cys191 is S-palmitoylated and that palmitoylation is required for pore formation. S-palmitoylation, which does not affect GSDMD cleavage, is augmented by mitochondria-generated reactive oxygen species (ROS).

The palmitoylation of gasdermin D directs its membrane translocation and pore formation during pyroptosis.

Plasma membrane perforation elicited by caspase cleavage of the gasdermin D (GSDMD) N-terminal domain (GSDMD-NT) triggers pyroptosis. The mechanisms underlying GSDMD membrane translocation and pore formation are not fully understood. Here, using a proteomic approach, we identified fatty acid synthase (FASN) as a GSDMD-binding partner.

Process Mass Intensity (PMI): A Holistic Analysis of Current Peptide Manufacturing Processes Informs Sustainability in Peptide Synthesis.

Small molecule therapeutics represent the majority of the FDA-approved drugs. Yet, many attractive targets are poorly tractable by small molecules, generating a need for new therapeutic modalities. Due to their biocompatibility profile and structural versatility, peptide-based therapeutics are a possible solution.

Gasdermin E dictates inflammatory responses by controlling the mode of neutrophil death.

Both lytic and apoptotic cell death remove senescent and damaged cells in living organisms. However, they elicit contrasting pro- and anti-inflammatory responses, respectively. The precise cellular mechanism that governs the choice between these two modes of death remains incompletely understood.

Palmitoylation of gasdermin D directs its membrane translocation and pore formation in pyroptosis.

Unlabelled: Gasdermin D (GSDMD)-mediated macrophage pyroptosis plays a critical role in inflammation and host defense. Plasma membrane perforation elicited by caspase-cleaved GSDMD N-terminal domain (GSDMD-NT) triggers membrane rupture and subsequent pyroptotic cell death, resulting in release of pro-inflammatory IL-1β and IL-18. However, the biological processes leading to its membrane translocation and pore formation are not fully understood.

Perioperative antimicrobial prophylaxis in clean-contaminated head and neck squamous cell cancer surgeries: Is less better?

Introduction: Judicious use of antibiotics and stringent adherence to practice guidelines is the need of the hour as antibiotic resistance is a rampant problem. Despite several reports in the literature describing the optimal duration of antibiotics, there is no consensus. A "one for all" protocol may be impractical and hence the guidelines need to be tweaked to take into consideration local factors.

Syndrome Valentino From a De Novo Aetiology - Acute Pancreatitis.

Valentino syndrome is one of the rare classical presentations of duodenal perforation, wherein the leaked contents collect at the right lower quadrant of the abdomen causing local peritonitis and mimicking appendicitis. Here we present a case profile of a 28-year-old gentleman, who presented with right lower quadrant abdominal pain and mass, which was clinically diagnosed as acute appendicular inflammatory mass. Later with laboratory reports and radiological imaging, he was confirmed to have acute pancreatitis, and actually the peripancreatic fluid collection has tracked down into the right iliac fossa and pelvis to present similar to Valentino syndrome.

MicroRNA-432-5p regulates sprouting and intussusceptive angiogenesis in osteosarcoma microenvironment by targeting PDGFB.

Osteosarcoma (OS) is a type of bone tumor conferred with high metastatic potential. Attainable growth of tumors necessitates functional vasculature mediated by sprouting angiogenesis (SA) and intussusceptive angiogenesis (IA). However, the regulation of IA and SA is still unclear in OS.

Parathyroid hormone-induced down-regulation of miR-532-5p for matrix metalloproteinase-13 expression in rat osteoblasts.

Parathyroid hormone (PTH) acts on osteoblasts and functions as an essential regulator of calcium homeostasis and as a mediator of bone remodeling. We previously reported that PTH stimulates the expression of matrix metalloproteinase-13 (MMP-13) in rat osteoblasts and that MMP-13 plays a key role in bone remodeling, endochondral bone formation, and bone repair. Recent evidence indicated that microRNAs (miRNAs) have regulatory functions in bone metabolism.

Characterization of Runx2 phosphorylation sites required for TGF-β1-mediated stimulation of matrix metalloproteinase-13 expression in osteoblastic cells.

Transforming growth factor-beta1 (TGF-β1), a highly abundant growth factor in skeletal tissues, stimulates matrix metalloproteinase-13 (MMP-13) expression in osteoblastic cells. MMP-13 plays a critical role in bone remodeling. Runx2, a bone transcription factor, is required for TGF-β1-mediated stimulation of MMP-13 expression in osteoblastic cells.

Evaluating the efficacy of memantine on improving cognitive functions in epileptic patients receiving anti-epileptic drugs: A double-blind placebo-controlled clinical trial (Phase IIIb pilot study).

Objectives: People with epilepsy have greater cognitive and behavioral dysfunction than the general population. There is no specific treatment available for cognitive impairment of these patients. We aimed to evaluate the effects of memantine, an N-methyl-D-aspartate-type glutamate receptor noncompetitive antagonist, on improving cognition and memory functions in epileptic patients with cognitive and memory impairment, who received anti-epileptic drugs (AEDs).

Recurrence patterns and management options in aggressive fibromatosis.

Aggressive fibromatosis is a rare neoplasm arising from musculoaponeurotic structures. Our aim is to share our experience with this rare tumor in our institute and to discuss the more perplexing recurrence patterns and the management options. This is a retrospective study of the disease, treated in our institute for the past fourteen years.

Successful treatment of Strongyloides stercoralis hyperinfection in a case of systemic lupus erythematosus - review of the literature regarding various treatment schedules.

Strongyloides stercoralis hyperinfection poses a great challenge to physicians in the tropics due to their non-specific symptoms and signs. Early identification and initiation of treatment improves mortality rates. Reports of Strongyloides infection in Hansens disease, systemic lupus erythematosus (SLE), organ transplant recipients and malnourished individuals have been reported in the published literature.

Limb conservation in extremity soft tissue sarcomas with vascular involvement.

Background: The major neurovascular involvement and large primary tumors are indication of amputation. The present study is an attempt to explore the feasibility of a limb salvage surgery in extremity sarcoma cases with major vessel involvement. Oncological outcomes and surgery-related morbidities are compared with those reported in literature.