Cold Inducible RNA-Binding Protein Promotes the Development of Alzheimer's Disease Partly by Inhibition of uPA in Astrocytes.

Background: Cold inducible RNA-binding protein (CIRP) is an important danger-associated molecular pattern involved in tissue-specific and systemic inflammation related to inflammation and Alzheimer's disease (AD). However, the precise roles and mechanism of CIRP in the functional changes in astrocytes during the development of AD are still unknown. This study aimed to assess gene expression alterations in astrocytes after they overexpress CIRP (oe-CIRP) and to explore the relationship between abnormal CIRP expression and AD.

Xuebijing Injection Promotes M2 Polarization of Macrophages and Improves Survival Rate in Septic Mice.

Xuebijing (XBJ) injection, a concoction of several Chinese herbs, has been widely used as an immunomodulator for the treatment of severe sepsis in China. However, the precise mechanisms responsible for its efficacy have not been fully elucidated. In our study, we determined the flow cytometry markers (F4/80, CD11c, and CD206), the levels of secreted cytokines (TNF-α, IL-6, and IL-10), and the expression of specific proteins of M2 (Ym1, Fizz1, and Arg1) to assess macrophage polarization.

Ischemia-reperfusion induces renal tubule pyroptosis via the CHOP-caspase-11 pathway.

The apoptotic or necrotic death of renal tubule epithelial cells is the main pathogenesis of renal ischemia-reperfusion-induced acute kidney injury (AKI). Pyroptosis is a programmed cell death pathway that depends on the activation of the caspase cascade and IL-1 cytokine family members. However, the role of pyroptosis in AKI induced by ischemia-reperfusion remains unclear.

Effect of high mobility group box-1 protein on immune cells and its regulatory mechanism.

High mobility group box-1 protein (HMGB1), which is a nuclear protein, participates in chromatin architecture and transcriptional regulation. When released from cells, HMGB1 also plays a well-established role as a pro-inflammatory mediator during innate immune responses to injury. In the initial stage of injury, there is a release of large quantities of early pro-inflammatory mediators to initiate or perpetuate immune responses against pathogens, but this pro-inflammatory period is transient, and it is followed by a prolonged period of immune suppression.

Endoplasmic reticulum stress and its regulator XBP-1 contributes to dendritic cell maturation and activation induced by high mobility group box-1 protein.

High mobility group box-1 protein (HMGB1) had been proved to induce maturation and activation of dendritic cell (DC), however, the endogenous changes and mechanisms underlying are unknown. Since endoplasmic reticulum stress (ERS) activates an adaptive unfolded protein response (UPR) that facilitates cellular survival and repair, we hypothesized that HMGB1 may regulate the function of DC by modulating ERS. In our study, HMGB1 stimulation induced significant ERS responses in DCs in a time- and dose-dependent manner, demonstrated by the up-regulation of a number of ERS markers.

[Influence of splenic high mobility group box-1 protein on immune function of regulatory T lymphocytes in scald rats].

Objective: To observe the influence of high mobility group box-1 protein (HMGB1) derived from spleen on the phenotype of regulatory T lymphocytes (Treg) and HMGB1-mediated immune function in severely scalded rats after delayed resuscitation.

Methods: One hundred and four Wistar rats were divided into normal control group (NC, n = 8), sham scald group (SS, n = 32), scald group (S, n = 32), and ethyl pyruvate (EP) treatment group (EPT, n = 32) according to the random comparison table. Rats in the latter 2 groups were subjected to 30%TBSA full-thickness scald, which were intraperitoneally injected with Ringer solution or EP solution at post scald hour (PSH) 6 (delayed antishock treatment) and administered with 4 mL Ringer solution or EP solution per 12 hours after PSH 12 till PSH 48.

Association between high-mobility group box-1 protein release and immune function of dendritic cells in thermal injury.

The present study was performed to investigate in vivo the effect of high-mobility group box-1 protein (HMGB1) on the maturation of dendritic cell (DC) and the influence on T-cell-mediated immunity after thermal injury. Rats were randomly divided into 3 groups as follows: sham burn group, burn group, and burn with ethyl pyruvate (EP) treatment group, and they were sacrificed on post burn days (PBD) 1, 3, 5, and 7 respectively. MACS microbeads were used to isolate splenic DCs and column of nylon wool to obtain T cells.

[The pattern of nuclear factor-kappaB activation in rats with endotoxin shock and its role in biopterin-mediated nitric oxide induction].

Objective: To investigate the pattern of nuclear factor-kappaB (NF-kappaB) activation in rats with lipopolysaccharide( LPS) shock, and to explore the mechanism of NF-kappaB signal pathway in the biopterin-mediated nitric oxide(NO) induction, as well as its role in the development of multiple organ dysfunction syndrome ( MODS) secondary to endotoxin challenge.

Methods: Fourty-seven male Wistar rats were randomly divided into control group ( C, n = 8) , LPS group ( n = 24, with 8 rats at each time-points, and shock model was made by injection of same dosage of LPS) , and pyrrolidine dithiocarbamate (PDTC) treatment group ( PDTC, n = 15, with 5 rats at each time-points, and the rats were injected with LPS and PDTC). The rats were sacrificed at 2,6,12 post-injection hour( PIH) , and the blood and tissue samples from liver, lungs and kidneys were harvested for the determination of NF-KB activity, GTP cyclohydrolase I (GTP-CH I ) , and inducible nitric oxide synthase (iNOS) mRNA expression in the liver, lungs and kidneys, plasma and tissue content of biopterin and NO, as well as hepatic and renal function, and pulmonary myeloperoxidase activity.

[Relationship between nuclear factor-kappaB activity and kidney injury in rats with postburn sepsis].

Objective: To investigate the relationship between nuclear factor-KappaB (NF-KappaB) activity and kidney injury in rats with postburn sepsis.

Methods: Rats subjected to 30% full-thickness scald injury, followed by intraperitoneal injection of lipopolysaccharide (LPS), were used in the present study. Fifty-four Wistar rats were randomly divided into normal control group, postburn sepsis 1, 2, 6, 12, 24 hours groups, and sepsis with NF-KappaB inhibitor pyrrolidine dithiocarbamate (PDTC) treatment 1, 2, and 6 hour groups.

[The mechanisms of extracellular-signal regulated protein kinase pathway in biopterin induction in rats with endotoxic shock].

Objective: To observe the influence of treatment with the inhibitor of extracellular-signal regulated protein kinase (ERK) signal transduction pathway on the expression of biopterin/nitric oxide (NO) as well as the activation of nuclear factor-kappaB (NF-kappaB), and to clarify the potential cross-talk regulation mechanisms between ERK and NF-kappaB pathway in biopterin-mediated NO induction in rats with endotoxic shock.

Methods: Using an endotoxic shock model, 60 male Wistar rats were randomly divided into normal controls (n = 8), endotoxic shock group (n = 32) and PD98059 treatment group (n = 20). At serial time points animals in each group were sacrificed, and tissue samples from liver, lungs as well as kidneys were harvested to detect NF-kappaB activity, guanosine triphosphate-cyclohydrolase (GTP-CHI) and inducible nitric oxide synthase (iNOS) mRNA expression.

[Changes in Toll-like receptor 2 and 4 gene expression in vital organs in septic rats and their regulation mechanisms].

Objective: To investigate the changes in Toll-like receptor (TLR) 2 and 4 gene expression in vital organs in septic rats and their potential regulation mechanism.

Methods: One hundred Wistar rats were randomly divided into normal controls (n=10), sham-operated group (n=10), septic group (n=60), and recombinant bactericidal/permeability increasing protein (BPI)-treated group (n=20). Severe sepsis was replicated by cecal ligation and puncture (CLP).