Correction: Cell Therapy: A Safe and Efficacious Therapeutic Treatment for Alzheimer's Disease in APP+PS1 Mice.

[This corrects the article DOI: 10.1371/journal.pone.

LRRK2 is required for CD38-mediated NAADP-Ca signaling and the downstream activation of TFEB (transcription factor EB) in immune cells.

CD38 is a cell surface receptor capable of generating calcium-mobilizing second messengers. It has been implicated in host defense and cancer biology, but signaling mechanisms downstream of CD38 remain unclear. Mutations in LRRK2 (leucine-rich repeat kinase 2) are the most common genetic cause of Parkinson disease; it is also a risk factor for Crohn disease, leprosy, and certain types of cancers.

AKT Regulates NLRP3 Inflammasome Activation by Phosphorylating NLRP3 Serine 5.

The cytosolic pattern recognition receptor NLRP3 senses host-derived danger signals and certain microbe-derived products in both humans and rodents. NLRP3 activation assembles an inflammasome complex that contains the adapter proteins ASC and caspase-1, whose activation triggers the maturation and release of the proinflammatory cytokines IL-1β and IL-18. S5 phosphorylation of NLRP3 prevents its oligomerization and activation, whereas dephosphorylation of this residue by the phosphatase PP2A allows NLRP3 activation.

SARS-Coronavirus Open Reading Frame-8b triggers intracellular stress pathways and activates NLRP3 inflammasomes.

The SARS (severe acute respiratory syndrome) outbreak was caused by a coronavirus (CoV) named the SARS-CoV. SARS pathology is propagated both by direct cytotoxic effects of the virus and aberrant activation of the innate immune response. Here, we identify several mechanisms by which a SARS-CoV open reading frame (ORF) activates intracellular stress pathways and targets the innate immune response.

Inflammasome Inhibition Links IRGM to Innate Immunity.

IRGM is a risk factor for several inflammatory diseases, yet no direct link to immune regulation had been shown. In this issue of Molecular Cell, Mehto et al. (2019) report that IRGM limits NLRP3 inflammasome activation-by both direct inhibition of NLRP3/ASC oligomerization and selective autophagic destruction of NLRP3/ASC.

Gα Signaling Regulates Inflammasome Priming and Cytokine Production by Biasing Macrophage Phenotype Determination.

Macrophages exist as innate immune subsets that exhibit phenotypic heterogeneity and functional plasticity. Their phenotypes are dictated by inputs from the tissue microenvironment. G-protein-coupled receptors are essential in transducing signals from the microenvironment, and heterotrimeric Gα signaling links these receptors to downstream effectors.

Inhibition of Ctsk alleviates periodontitis and comorbid rheumatoid arthritis via downregulation of the TLR9 signalling pathway.

Aim: In this study, we investigate the mechanistic link between rheumatoid arthritis (RA) and periodontitis to identify a novel target (cathepsin K; Ctsk) for the treatment of comorbid periodontitis and RA.

Methods: An experimental model of periodontitis with arthritis was established in DBA/1 mice. We then tested the effect of BML-244, a specific inhibitor of Ctsk, by quantifying several inflammatory markers of TLR9 signalling both in vivo and in vitro.

The comparison of biocompatibility and osteoinductivity between multi-walled and single-walled carbon nanotube/PHBV composites.

The applications of poly (3-hydroxybutyrate-co-3-hydroxyvalerate) (PHBV) in tissue engineering have been widely studied. This study aimed to compare the biocompatibility and osteoinductivity of single-walled carbon nanotubes (SWCNTs)/PHBV composites with multi-walled CNTs (MWCNTs)/PHBV composites. CNTs were dispersed in PHBV by ultrasonication and composites were created using thermal injection moulding.

SARS-Coronavirus Open Reading Frame-3a drives multimodal necrotic cell death.

The molecular mechanisms underlying the severe lung pathology that occurs during SARS-CoV infections remain incompletely understood. The largest of the SARS-CoV accessory protein open reading frames (SARS 3a) oligomerizes, dynamically inserting into late endosomal, lysosomal, and trans-Golgi-network membranes. While previously implicated in a non-inflammatory apoptotic cell death pathway, here we extend the range of SARS 3a pathophysiologic targets by examining its effects on necrotic cell death pathways.

Inhibition of angiotensin II receptor I prevents inflammation and bone loss in periodontitis.

Background: Periodontal disease is characterized by alveolar bone destruction and degenerative lesions of the periodontal ligament (PDL); it is initiated by bacterial infection of the oral cavity, but the clinical effects are secondary to an aberrant host immune response. Primary hypertension (PH), which causes significant morbidity and mortality worldwide, has also been shown to be an inflammatory disease characterized by aberrant immune cell infiltration and activation. Clinical retrospective studies have shown a link between PH and periodontitis with PH exacerbating periodontitis and vice versa, but the pathophysiologic mechanisms responsible for this remain unknown.

LOX-related collagen crosslink changes act as an initiator of bone fragility in a ZDF rats model.

Diabetes mellitus type 2 (DM2) results in bone abnormalities that manifest as increased bone fragility. Bone consists of two phases, the mineral phase and the matrix phase, and disorders in both are seen in DM2. However, the phase in which DM2 mediated bone fragility is initiated is still unknown.

The Transcription Factor EB Links Cellular Stress to the Immune Response .

The transcription factor EB (TFEB) is the master transcriptional regulator of autophagy and lysosome biogenesis. Recent advances have led to a paradigm shift in our understanding of lysosomes from a housekeeping cellular waste bin to a dynamically regulated pathway that is efficiently turned up or down based on cellular needs. TFEB coordinates the cellular response to nutrient deprivation and other forms of cell stress through the lysosome system, and regulates a myriad of cellular processes associated with this system including endocytosis, phagocytosis, autophagy, and lysosomal exocytosis.

Autophagy and inflammasomes.

Autophagy is a ubiquitous cellular mechanism for the targeted lysosomal degradation of various cytosolic constituents, from proteins to organelles. As an essential homeostatic mechanism, autophagy is upregulated in response to numerous environmental and pharmacological stimuli, including starvation, where it facilitates the recycling of essential amino acids. In addition, autophagy plays specific roles within the immune system; it serves as a source of peptides for antigen presentation, a mechanism for the engulfment and degradation of intracellular pathogens and as a key regulator of inflammatory cytokines.

Low-intensity pulsed ultrasound upregulates pro-myelination indicators of Schwann cells enhanced by co-culture with adipose-derived stem cells.

Objectives: Peripheral nerve injuries are a common occurrence, resulting in considerable patient suffering; it also represents a major economic burden on society. To improve treatment options following peripheral nerve injuries, scientists aim to find a way to promote Schwann cell (SC) myelination to help nerves to carry out their functions effectively. In this study, we investigated myelination ability of SCs, regulated by co-culture with adipose-derived stem cells (ASCs) or low-intensity pulsed ultrasound (LIPUS), and synergistic effects of combined treatments.

Cell therapy: a safe and efficacious therapeutic treatment for Alzheimer's disease in APP+PS1 mice.

Previously, our lab was the first to report the use of antigen-sensitized dendritic cells as a vaccine against Alzheimer's disease (AD). In preparation of this vaccine, we sensitized the isolated dendritic cells ex vivo with Aβ peptide, and administered these sensitized dendritic cells as a therapeutic agent. This form of cell therapy has had success in preventing and/or slowing the rate of cognitive decline when administered prior to the appearance of Aβ plaques in PDAPP mice, but has not been tested in 2 × Tg models.

Modification of rat model of sciatica induced by lumber disc herniation and the anti-inflammatory effect of osthole given by epidural catheterization.

One of the most treatable causes of lower back pain and associated sciatica is lumbar disc herniation (LDH), which is characterized by rupture of the hard outer wall (annulus fibrosis) in a lumbar intervertebral disc. In the current study, we aimed to: (1) develop and characterize a rat model of sciatica induced by LDH, while introducing a novel method of epidural catheterization; (2) use this model to evaluate the effect of osthole on pain due to LDH, and (3) gain insight into the mechanisms through which osthole affects sciatica induced by LDH. The results indicate that our newly developed rat model maintained mechanical allodynia for 28 days without reduction.

Proteomic response to acupuncture treatment in spontaneously hypertensive rats.

Previous animal and clinical studies have shown that acupuncture is an effective alternative treatment in the management of hypertension, but the mechanism is unclear. This study investigated the proteomic response in the nervous system to treatment at the Taichong (LR3) acupoint in spontaneously hypertensive rats (SHRs). Unanesthetized rats were subject to 5-min daily acupuncture treatment for 7 days.

Efficacy of a therapeutic vaccine using mutated β-amyloid sensitized dendritic cells in Alzheimer's mice.

Despite FDA suspension of Elan's AN-1792 amyloid beta (Aβ) vaccine in phase IIb clinical trials, the implications of this study are the guiding principles for contemporary anti-Aβ immunotherapy against Alzheimer's disease (AD). AN-1792 showed promising results with regards to Aβ clearance and cognitive function improvement, but also exhibited an increased risk of Th1 mediated meningoencephalitis. As such, vaccine development has continued with an emphasis on eliciting a notable anti-Aβ antibody titer, while avoiding the unwanted Th1 pro-inflammatory response.