Expression of MSP58 in hepatocellular carcinoma.

We have investigated the expression and role of the 58-kDa micro-spherule protein (MSP58) in hepatocellular carcinoma (HCC). Immunohistochemistry was performed in 252 samples from patients with HCC to detect the expression level of MSP58. Results indicated that the expression level of MSP58 in the cancer samples was significantly higher than that in adjacent normal tissues. The Wilcoxon-Mann-Whitney test showed significant difference in the expression of MSP58 in patients with serum AFP, tumor size, histological differentiation, and universal integrated circuit card (UICC) stage (P < 0.001, P = 0.004, P < 0.001, P < 0.001, respectively). A total of 252 HCC patients were followed up for five consecutive years, and Kaplan-Meier survival analysis demonstrated that the survival time of HCC patients with low expression of MSP58 was longer than those with high expression during the 5-year follow-up period (P < 0.001). Cox regression analysis indicated that high expression of MSP58 (++ or +++), serum AFP (≥25 µg/L), tumor size (≥3 cm), and UICC stage (III or IV) were the independent poor prognostic factors of HCC (P = 0.008, 0.0290, 0.001, 0.047, respectively). Furthermore, down-regulation of MSP58 was introduced to HCC cell lines (HepG2 and Huh7) by plasmid transfection. In vivo and in vitro studies indicated that MSP58si markedly reduced proliferation and promoted the apoptosis of HepG2 and Huh7 cells. In summary, our results demonstrated that MSP58 played an important role in the proliferation and apoptosis of HCC cells and the expression of MSP58 in HCC patients was closely related to the prognosis.

Topographical distributions of endomorphinergic pathways from nucleus tractus solitarii to periaqueductal gray in the rat.

In the central nervous system (CNS), endomorphin 1 (EM1)- and endomorphin 2 (EM2)-containing neuronal cell bodies have been found in the nucleus tractus sollitarii (NTS) and the hypothalamus, and EMergic fibers and terminals are distributed widely in many regions of the CNS, including the periaqueductal gray (PAG). The aim of the present study was to examine whether EM-expressing neurons in the NTS of the rat send their axons to the PAG, and determine whether the EMergic pathway from the NTS to the PAG is topographic by using. Immunofluorescent staining for EM1 or EM2 combined with retrograde and anterograde tract-tracing methods. The results showed that after injecting tetramethyl rhodamine dextran-amine (TMR) into the ventrolateral or lateral column of the PAG, some EM1- or EM2-immunoreactive (IR) neurons in the NTS were retrogradely labeled with TMR, and the majority of the EM-IR/TMR double-labeled neurons were mainly distributed in the medial and commissural subnuclei of the NTS. Following injection of biotinylated dextran amine (BDA) into the medial or commissural subnucleus of the NTS, EM1-IR/BDA and EM2-IR/BDA double-labeled fibers and terminals were mainly distributed in the ventrolateral or lateral column of the PAG, respectively. The results indicate that EMergic pathway from the NTS to PAG is topographically organized, and suggest that EMs released from NTS to PAG projecting terminals may bind to mu-opioid receptor on the PAG neurons, and thereby contribute to various functions.

CB1 cannabinoid receptor participates in the vascular hyporeactivity resulting from hemorrhagic shock in rats.

BACKGROUND: Vascular hyporeactivity, which occurs in the terminal stage of hemorrhagic shock, is believed to be critical for treating hemorrhagic shock. The present study was designed to examine whether the CB1 cannabinoid receptor (CB1R) was involved in the development of vascular hyporeactivity in rats suffering from hemorrhagic shock. METHODS: Sixteen animals were randomly divided into two groups (n = 8 in each group): sham-operated (Sham) and hemorrhagic shock (HS) groups. Hemorrhagic shock was induced by bleeding. The mean arterial pressure (MAP) was reduced to and stabilized at (25 +/- 5) mmHg for 2 hours. The vascular reactivity was determined by the response of MAP to norepinephrine (NE). In later experiments another twelve animals were used in which the changes of CB1R mRNA and protein in aorta and superior mesenteric artery (SMA) were analyzed by RT-PCR and Western blotting. In addition, we investigated the effects of a CB1R antagonist on the vascular hyporeactivity and survival rates in rats with hemorrhagic shock. Survival rates were analyzed by the Fisher's exact probability test. The MAP response was analyzed by one-way analysis of variance (ANOVA). RESULTS: Vascular hyporeactivity developed in all animals suffering from hemorrhagic shock. The expression of CB1R mRNA and protein in aorta and 2 - 3 branches of the SMA were significantly increased in the HS group after the development of vascular hyporeactivity when compared to those in Sham group. When SR141716A or AM251 was administered, the MAP response to NE was (41.75 +/- 4.08) mmHg or (44.78 +/- 1.80) mmHg respectively, which was higher than that in saline groups with (4.31 +/- 0.36) mmHg (P < 0.01). We also showed an increased 4-hour survival rate in the SR141716A or AM251-treated group with 20% or 30%, but with a statistically significant difference present between the AM251-treated and saline groups (P < 0.05). CONCLUSIONS: CB1R is involved in vascular hyporeactivity resulting from hemorrhagic shock in rats, and CB1R antagonist may be useful in treating patients with traumatic, hemorrhagic shock who need field-rescue or initial treatment.

Severity of sepsis is correlated with the elevation of serum high-mobility group box 1 in rats.

BACKGROUND: Sepsis is a leading cause of death in the intensive care units. The late inflammatory cytokine, high-mobility group box 1 (HMGB1), plays a critical role in sepsis. In the present study, we investigated the association between the serum HMGB1 levels and the severity of organ injury in the lipopolysaccharide-induced sepsis in rats. METHODS: To produce an animal model of sepsis with different degree of organ injury, animals were treated with three different doses of lipopolysaccharide (4, 8 and 16 mg/kg), and the animals in control group were treated with the same volume of the vehicle (saline). The levels of serum HMGB1 were measured at 0, 2, 4, 8, 16, 24, 32 and 48 hours after lipopolysaccharide (LPS) or vehicle injection, meanwhile the biochemical and histopathological indicators for the severity of organ injury were assessed. RESULTS: The level of HMGB1 had a positive, high correlation with the abnormal changes of serum cardiac troponin I, alanine aminotransferase, aspartate aminotransferase, creatinine and blood urea nitrogen, as well as the pathologic scores of heart, lung, liver and kidney. CONCLUSIONS: The level of serum HMGB1 is highly correlated with the severity of sepsis in rats, suggesting that HMGB1 could serve as a valuable adjunct in the diagnosis and management of sepsis.

[Effect of dopamine combined with norepinephrine on the renal function in patients with septic shock].

OBJECTIVE: To investigate the effects of dopamine and norepinephrine on the renal function in the patients with septic shock. METHODS: Eighty-seven patients with septic shock were divided into three groups (group A, B, C) according to the biggest infusing rate of norepinephrine, with the infusing rate of 0.5 - 0.9, 1.0 - 1.5, 1.6 - 2.0 microg x kg(-1) x min(-1), respectively. Mean arterial blood pressure (MAP), heart rate (HR), urine output, blood urea nitrogen (BUN), creatinine (CRE), urine albumin (U-ALB) and urine beta(2)-microglobulin (Ubeta(2)-MG) as well as APACHE III score in all the patients were detected. RESULTS: Before anti-shock therapy was given, hypotension, tachycardia and oliguria occurred in all the 87 patients, and CRE, BUN, U-ALB, Ubeta(2)-MG and APACHE III score were abnormal in most cases. With the anti-shock therapy, MAP, HR, urine output and BUN, CRE in all patients returned to normal levels gradually, and U-ALB, Ubeta(2)-MG levels and APACHE III score also restored but still remained abnormal. CONCLUSIONS: The first aim of treating septic shock should be restoring the organ blood supply, and based on volume resuscitation, dopamine, noradrenaline and other vasoactive drugs could be combined to maintain circulatory stability.