15-Deoxy-Δ12,14-prostaglandin J2 alleviates hepatic ischemia-reperfusion injury in mice via inducing antioxidant response and inhibiting apoptosis and autophagy.

Hepatic ischemia-reperfusion (I/R) injury is a common clinical impairment that occurs in many circumstances and leads to poor prognosis. Both apoptosis and autophagy have been shown to contribute to cell death in hepatic I/R injury. 15-Deoxy-Δ12,14-prostaglandin J2 (15d-PGJ2) is one of the best-studied anti-inflammatory prostaglandins, which has been verified to exert anti-inflammatory and cell-protective functions in various types of cells and animal models. In this study we explored the effects of 15d-PGJ2 on both apoptosis and autophagy in mouse hepatic I/R injury and its possible mechanisms. A model of segmental (70%) hepatic warm ischemia was established in Balb/c mice, and the pathological changes in serum and liver tissues were detected at 6, 12, and 24 h post-surgery, while 15d-PGJ2 (2.5, 7.5, 15 µg, iv) was administered 30 min prior the surgery. Pretreatment with 15d-PGJ2 (7.5, 15 µg) significantly ameliorated I/R-induced hepatic injury evidenced by dose-dependent reduction of serum ALT and AST levels as well as alleviated tissue damages. 15d-PGJ2 pretreatment significantly decreased the serum TNF-α and IL-1ß levels and the hepatic expression of F4/80, a major biomarker of macrophages. 15d-PGJ2 pretreatment upregulated the Bcl-2/Bax ratio, thus reducing the number of apoptotic cells in the livers. 15d-PGJ2 pretreatment considerably suppressed the expression of Beclin-1 and LC3, thus decreasing the number of autophagosomes in the livers. Furthermore, 15d-PGJ2 pretreatment activated Nrf2 and inhibited a ROS/HIF1α/BNIP3 pathway in the livers. Pretreatment with the PPARγ receptor blocker GW9662 (2 µg, ip) partly reversed the protective effects of 15d-PGJ2 on hepatic I/R injury. In conclusion, our results confirm the protective effect of 15d-PGJ2 on hepatic I/R injury, an effect that may rely on a reduction in the activation of Kupffer cells and on activation of the Nrf2 pathway, which lead to inhibition of ROS generation, apoptosis, and autophagy.

Meta-analysis of the efficacy of probiotics in Helicobacter pylori eradication therapy.

AIM: To evaluate the role of probiotics in the standard triple Helicobacter pylori therapy. METHODS: In this meta-analysis, we investigated the efficacy of probiotics in a standard triple H. pylori therapy in adults. Searches were mainly conducted in MEDLINE/PubMed, EMBASE, and the Cochrane Central Register of Controlled Trials. Fourteen studies met our criteria, and the quality of these studies was assessed using the Jadad scale. We used STATA version 12.0 to extract data and to calculate the odds ratios (ORs), which are presented with the corresponding 95% confidence intervals (CIs). The data are presented as forest plots. RESULTS: The pooled ORs for the eradication rates calculated by intention-to-treat analysis and per-protocol analysis in the probiotic group vs the control group were 1.67 (95%CI: 1.38-2.02) and 1.68 (95%CI: 1.35-2.08), respectively, using the fixed-effects model. The sensitivity of the Asian studies was greater than that of the Caucasian studies (Asian: OR = 1.78, 95%CI: 1.40-2.26; Caucasian: OR = 1.48, 95%CI: 1.06-2.05). The pooled OR for the incidence of total adverse effects was significantly lower in the probiotic group (OR = 0.49, 95%CI: 0.26-0.94), using the random effects model, with significant heterogeneity (I (2) = 85.7%). The incidence of diarrhea was significantly reduced in the probiotic group (OR = 0.21, 95%CI: 0.06-0.74), whereas the incidence of taste disorders, metallic taste, vomiting, nausea, and epigastric pain did not differ significantly between the probiotic group and the control group. CONCLUSION: Supplementary probiotic preparations during standard triple H. pylori therapy may improve the eradication rate, particularly in Asian patients, and the incidence of total adverse effects.

Sodium 3,5,6-trichloropyridin-2-ol poisoning: report of four cases.

Sodium 3,5,6-trichloropyridin-2-ol (STCP) is an important intermediate for synthesizing organophosphate insecticide chlorpyrifos. At present, chlorpyrifos is one of the world's largest species of pesticide products. Many studies have focused on the toxicity of chlorpyrifos, but few reports have looked at the toxicity mechanism of STCP. Even fewer studies have looked at STCP poisoning. With increasing production and usage of STCP, the chances of such poisoning will increase. In this study, we present a report on four workers who helped in the industrial manufacture of STCP and who were affected by exposure to it. We hope that these case studies will provide a foundation for further research into STCP.

[Expression of serum cytokines in patients with pneumoconiosis by antibody chip].

OBJECTIVE: To investigate the changes in expression of serum cytokines in patients with pneumoconiosis using cytokine antibody chips (CACs). METHODS: The CAC technology was applied to measure the serum levels of 60 cytokines in 12 patients with pneumoconiosis and 3 normal controls. RESULTS: In the patients with pneumoconiosis, the highly expressed serum cytokines included interleukin (IL)-1α, IL-1ß, IL-2, ILs 4-16, macrophage colony-stimulating factor, interferon-γ, tumor necrosis factor (TNF)-α, TNF-ß, human bone morphogenetic protein-6, fibroblast growth factor-7, neurotrophin-3, and stem cell factor, and the lowly expressed serum cytokines included recombinant human I-309, monocyte chemoattractant protein (MCP)-1, MCP-2, MCP-3, MCP-4, macrophage inflammatory protein (MIP)-1-δ, and MIP-3-α. CONCLUSION: Patients with pneumoconiosis have changes in the expression of most serum cytokines.

[Application of auditory brainstem response (ABR) and 40 Hz auditory event related potential (40 Hz AERP) to the diagnosis of occupational noise-induced hearing impairment].

OBJECTIVE: To investigate the application of auditory brainstem response (ABR) and 40 Hz auditory event related potential (40 Hz AERP) to the diagnosis of occupational noise-induced hearing impairment and to provide the evidence for diagnosis of occupational deafness. METHODS: Pure tone audiometry, ABR and 40 Hz AERP were performed in 54 workers occupationally exposed to noise. The thresholds of higher frequency band, 3 kHz and 4 kHz were compared with the threshold of ABR. The thresholds of auditory frequency ban and 0.5 kHz were compared with the threshold of 40 Hz AERP. RESULTS: A better correlation was found between thresholds of ABR and higher frequency pure tone audiometry. There was a significant difference of thresholds between 40 kHz AERP and pure tone audiometry. The correction values of thresholds between 40 kHz AERP and pure tone audiometry in the light noise-induced hearing impairment group and the moderate noise-induced hearing impairment group were (16.43 ± 1.08) and (11.80 ± 1.12) dBn HL, respectively. CONCLUSION: In diagnosis of occupational noise-induced hearing impairment, the threshold of ABR can be used to estimate the hearing threshold of pure noise higher frequency. Because there is the significant difference of the thresholds between pure tone audiometry and 40 Hz AERP, the response threshold can not be served as the audiometry threshold, and the behavioral hearing thresholds can only be obtained by adjusting the response threshold with respective correction value.

[Evaluating the effects of different oxygen therapies on the rats with acute nitrogen asphyxia].

OBJECTIVE: To Evaluate the effects of different oxygen therapies on the rats with acute nitrogen asphyxia and to study the best oxygen therapic protocol for patients with acute nitrogen asphyxia on the spot. METHODS: Sixty healthy male Wistar rats were divided into 5 groups: control, exposure to nitrogen, 33% oxygen treatment, 50% oxygen treatment and hyperbaric oxygen treatment groups. The behavioral performance, arterial oxygen pressure (PO2), carbon dioxide partial pressure (PCO2) and oxygen saturation (SPO2), biochemical changes in liver and kidney function and myocardial enzymes in 5 groups were measured. RESULTS: The rats exposed to nitrogen firstly were excited then inactive symptoms, but consciousness was recovered after oxygen therapy. The PO2 and SPO2 in nitrogen exposure group were (79.67 +/- 9.12) and (94.92 +/- 2.78) mm Hg, respectively, which were significantly lower than those in control group (P<0.01). The PO2 and SPO2 of 3 oxygen treatment groups were (94.75 +/- 7.24), (94.92 +/- 8.98), (104.58 +/- 7.12)mm Hg and (97.17 +/- 0.83), (96.92 +/- 1.16), (97.42 +/- 0.67)mm Hg, respectively, which were significantly higher than those in nitrogen exposure group (P<0.05). The PO2 in hyperbaric oxygen treatment group was significantly higher than those in other 2 oxygen treatment groups (P<0.05). The SPO2 in hyperbaric oxygen treatment group was (51.42 +/- 6.60) mm Hg which was significantly higher than that [(44.58 +/- 3.42)mm Hg] in 50% oxygen treatment groups (P< 0.05). AST [(270.50 +/- 49.05 )U/L], ALT [(122.67 +/- 55.44 )U/L], BUN [(7.31 +/- 0.93 )mmol/L], Cr[(28.32 +/- 4.35) micromol/L], CK [(1808.42 +/- 582.05)U/L] and CtnI [(22.52 +/- 14.29 )ng/ml] in nitrogen exposure group were significantly higher than those in control group (P<0.05). AST [(165.25 +/- 30.87) U/L], HBDH [(350.83 +/- 103.00)U/L] and CtnI [(11.23 +/- 5.38) ng/ml] in hyperbaric oxygen treatment group were significantly lower than those in other 2 oxygen treatment groups (P<0.05). CONCLUSION: Timely and effective oxygen therapy can significantly increase arterial pressure of oxygen and oxygen saturation in the rats with acute nitrogen asphyxia, and can improve liver function and cardiac damage. The hyperbaric oxygen chamber can significantly increase the therapeutic effects on rats with acute nitrogen asphyxiation.

[Evaluation of different oxygen therapies on therapeutic effects in rats with acute carbon dioxide poisoning].

OBJECTIVE: To study therapeutic effects by using different oxygen therapies in rats with acute carbon dioxide poisoning, to select the best oxygen therapy technology for patients with acute carbon dioxide poisoning on the spot. METHODS: Sixty healthy male Sprague-Dawley rats were randomized into normal control group, carbon dioxide exposure group, hyperbaric oxygen treatment group (pressure 2 ATA, FiO(2)100%), high concentration of atmospheric oxygen treatment group (FiO(2)50%), low concentration of atmospheric oxygen treatment group (FiO(2)33%). After treated with different oxygen in rats with acute carbon dioxide poisoning, arterial pH, PO2 and PCO2 of rats were detected, in addition observe pathological changes of lung tissue and brain tissue. RESULTS: The arterial pH (7.31 ± 0.06) and PO2 [(68.50 ± 15.02) mm Hg] of carbon dioxide exposure group were lower than those of control group [pH (7.42 ± 0.02) and PO2 (92.83 ± 8.27) mm Hg], PCO2 [(71.66 ± 12.10) mm Hg] was higher than that of control group [(48.25 ± 2.59) mm Hg] (P < 0.05); the arterial pH (hyperbaric oxygen treatment group 7.37 ± 0.02, high concentration of atmospheric oxygen treatment group 7.39 ± 0.03, low concentration of atmospheric oxygen treatment group 7.38 ± 0.02) and PO2 of oxygen treatment groups [hyperbaric oxygen treatment group, high concentration of atmospheric oxygen treatment group, low concentration of atmospheric oxygen treatment group were (82.25 ± 12.98), (84.75 ± 11.24), (83.75 ± 16.77) mm Hg, respectively] were higher than that of carbon dioxide exposure group, PCO2 [hyperbaric oxygen treatment group, high concentration of atmospheric oxygen treatment group, low concentration of atmospheric oxygen treatment group were (52.25 ± 4.95), (51.75 ± 4.82), (52.66 ± 5.61) mm Hg, respectively] was lower than that of carbon dioxide exposure group (P < 0.05); there was no significant difference of the arterial pH, PO2 and PCO2 between oxygen treatment groups and control group (P > 0.05); there was no significant difference of the arterial pH, PO2 and PCO2 among oxygen treatment groups (P > 0.05). There was large area of bleeding of lungs in rats with carbon dioxide poisoning, the bleeding of lungs in rats with high concentration of atmospheric oxygen treatment and low concentration of atmospheric oxygen treatment was better than the rats with carbon dioxide poisoning, there was no abnormal appearance of lungs in rats with hyperbaric oxygen treatment. The light microscope observation showed that there were diffuse bleeding and exudation of lungs in rats with carbon dioxide poisoning, the bleeding and exudation of lungs in rats with high concentration of atmospheric oxygen treatment and low concentration of atmospheric oxygen treatment were better than the rats with carbon dioxide poisoning, there were only minor bleeding and exudation of lungs in rats with hyperbaric oxygen treatment. There was no difference of brain in anatomy and microscopy among all groups, there were no significant bleeding, edema, cell degeneration and necrosis. CONCLUSIONS: Lung pathology in acute carbon dioxide poisoning rats with hyperbaric oxygen treatment is better than the rats with high concentration of atmospheric oxygen treatment and low concentration of atmospheric oxygen treatment, there is no significant difference of effect between high concentration of atmospheric oxygen treatment group and low concentration of atmospheric oxygen treatment group, however, the results of blood gas analysis and lung pathology than the exposure group improved, so qualified medical unit for hyperbaric oxygen therapy as soon as possible, hyperbaric oxygen treatment facilities in the absence of circumstances, the emergency treatment of early oxygen is also a good measure.

Increased expression of cellular repressor of E1A-stimulated gene (CREG) in gastric cancer patients: a mechanism of proliferation and metastasis in cancer.

BACKGROUND: The cellular repressor of E1A-stimulated genes (CREG), a secreted glycoprotein, has been studied with human embryonic carcinoma cells, vascular smooth muscle cells, and NIH3T3 fibroblasts. However, its relationship to tumor cell proliferation and metastasis has not been examined in human gastric cancers (GC) until now. AIM: To investigate the expression of CREG in GC and its association with GC cell proliferation and metastasis. METHODS: Forty-two cases of GCs, matched normal gastric tissues, and the human gastric cancer cell lines BGC-823, SGC-7901, MKN45, normal gastric mucosa cell line GES, and HUVEC cell line ECV304 were used to analyze CREG expression at the level of mRNA and protein. The expression of CREG was then further examined by immunohistochemistry in 42 GC tissues, and the correlation between the level of CREG and the pathological and clinical data was evaluated. Finally, we down-regulated the expression of CREG in GC cells with specific siRNA, and assessed the role of CREG in the proliferation and metastasis/invasion of the GC cell line. RESULTS: The level of CREG was found to be higher in malignant GC tissues and cells compared to adjacent normal tissues and normal gastric cells (p < 0.001). Additionally, the expression levels of CREG were positively correlated with tumor clinical stage (p = 0.001), tumor metastasis (p < 0.001), and stages of tumor infiltration (p = 0.019). Furthermore, by using siRNA, we found that the down-regulated expression of CREG inhibited the proliferation of GC cells (p < 0.05), and migration of both GC cells (p = 0.001). CONCLUSIONS: Our data suggest that CREG plays an important role in gastric cancer cell proliferation and metastasis and that CREG may be a potential therapeutic target for GC.

Down-regulation of miR-212 expression by DNA hypermethylation in human gastric cancer cells.

There has been few report discussing the expression and function of miR-212 in gastric cancer (GC). The aim of this pilot study was to investigate the expression of miR-212 in both gastric cancer tissues and gastric cancer cells and further explores the possible reasons for this change and the impact on the development of gastric cancer. qRT-PCR was used to detect the expression of miR-212 in primary GC tissues, adjacent normal tissues, gastric cancer cell lines BGC-823, SGC-7901, MKN-45, and normal gastric mucosa cell line GES. The expression of miR-212 was evaluated before and after treatment with methylation inhibitor-5-Aza-2'-deoxycitidine (5-Aza-dC), finally anti-miRNA and dual luciferase reporter assay were used to prove that MYC is a target gene of miR-212. The results showed that a significant reduction of miR-212 expression in GC tissues was observed compared to that in normal tissues (P = 0.002). At the same time, miR-212 expression level in normal gastric mucosa cell line GES was higher than that of in gastric cancer cell lines BGC-823, SGC-7901, and MKN-45 (P = 0.015, 0.008, 0.044, respectively). Computer sequence analysis showed the hypermethylation of CpG islands(CPI) in the promoter regions of miR-212 led to the lower expression of miR-212 in gastric cell strains (BGC-823 and SGC-7901). MiR-212 expression was significantly recovered after treatment with methylation inhibitor 5-Aza-dC (P = 0.016, 0.000, 0.015, respectively). Then, the results of AMOs transfection and dual luciferase reporter assay showed that Myc is a target of miR-212, which will be helpful to verify the function of miR-212 in carcinogenesis. The conclusion could be deduced from the study that decreased expression of miR-212 may be due to hypermethylation of CPI in gastric cancer cells, and miR-212 might act on the progression of gastric cancer through the potential target gene Myc.

Gli1 maintains cell survival by up-regulating IGFBP6 and Bcl-2 through promoter regions in parallel manner in pancreatic cancer cells.

BACKGROUND: Aberrant activation of Hedgehog (Hh) signaling pathway has been reported to be related to malignant biological behavior of pancreatic cancer but its mechanism is unclear yet. Since IGF pathway and Bcl-2 family are involved in proliferation and apoptosis of pancreatic cancer cells, we hypothesize that they are possibly associated with Hh pathway. MATERIALS AND METHODS: We studied the relationship of Shh-Gli1 signaling pathway with proliferation and apoptosis of pancreatic cancer cells and the regulation of transcription factor Gli1 to insulin-like growth factor binding protein 6 (IGFBP6) and Bcl-2 genes at the level of transcription. RESULTS: Sonic hedgehog (Shh), Smoothened (Smo), patched and Gli1 were expressed in pancreatic cancer cells. Cyclopamine inhibited cell proliferation at low concentration and induced apoptosis at high concentration. Effect of RNA interference (RNAi) for Gli1 to cell survival is mainly due to proliferation inhibition though involved in apoptosis. The transcription factor Gli1 bound to promoter regions of Bcl-2 and IGFBP6 genes and the levels of IGFBP6, proliferating cell nuclear antigen (PCNA) and Bcl-2 messenger RNA (mRNA) were decreased as well as Gli1 mRNA significantly by cyclopamine or RNAi in cultured pancreatic cancer cells (p < 0.01). Finally PCNA, IGFBP6 and Bcl-2 mRNA were upregulated as well as Shh or Gli1 in pancreatic cancer tissues (p < 0.01). CONCLUSIONS: Our study reveals that Gli1 maintained cell survival by binding the promoter regions and facilitating transcription of IGFBP6 and Bcl-2 genes in a parallel manner in pancreatic cancer cells and suggests it may be one of the mechanisms of Shh-Gli1 signaling pathway in pancreatic cancer.

Effect of Lianshu preparation on lipopolysaccharide-induced diarrhea in rats.

AIM: To investigate the effect of Lianshu preparation on lipopolysaccharide (LPS)-induced diarrhea in rats. METHODS: A diarrhea model was established in Sprague Dawley rats via injection of 1 mL of 30 mg/kg LPS. A total of 40 rats were randomly divided into normal group, LPS group, LPS + Lianshu group, LPS + berberine group (n = 10 in each group). Their intestinal mucosal barrier and frequency of diarrhea were observed. Levels of glucose, serum Na(+), K(+), Cl(-) and hematocrit, plasma nitrogen monoxide (NO), diamine oxidase (DAO), and D (-)-lactate were measured. The number of IgA+ plasma cells in small intestine was detected and SIgA levels in the intestinal fluid were measured. The antipyretic activity of Lianshu preparation in rats was evaluated using Brewer's yeast-induced pyrexia (10 mL/kg of 20% aqueous suspension). Acetaminophen (250 mg/kg, intragastric administration, bid) was used as a standard drug for comparison. Temperature was recorded 1 h before and 6 h after Brewer's yeast injection. Finally, small intestinal transmission in mice treated with Lianshu was detected after intraperitoneal injection of methyl prostigmin (2 mg/kg). Atropine (10 g/kg) was used as a control. The ink content in intestine was determined and the total length of intestine was measured. RESULTS: The frequency of diarrhea was higher in LPS group than in LPS + Lianshu group and LPS + berberine group (36.70 +/- 5.23 vs 28.50 +/- 4.06 and 32.70 +/- 9.30 respectively, P < 0.01), and lower in LPS + Lianshu group than in LPS + berberine group (P = 0.03). The levels of Na(+), glucose, Cl(-), K(+) were significantly lower in LPS + Lianshu group than in LPS + berberine group (140.35 +/- 3.19 mmol/L vs 131.99 +/- 4.86 mmol/L, 8.49 +/- 1.84 mmol/L vs 6.54 +/- 2.30 mmol/L, 106.29 +/- 4.41 mmol/L vs 102.5 +/- 1.39 mmol/L, 5.08 +/- 0.66 mmol/L vs 4.32 +/- 0.62 mmol/L respectively, P < 0.05). The level of hematocrit was lower in LPS + Lianshu group than in LPS + berberine group (0.50% +/- 0.07% vs 0.59% +/- 0.10% respectively, P < 0.05). The plasma levels of NO, DAO and D (-)-lactate were higher in LPS group than in normal group (79.74 +/- 7.39 micromol/L vs 24.94 +/- 3.38 micromol/L, 2.48 +/- 0.42 micro/mL vs 0.82 +/- 0.33 micro/mL, 5.63 +/- 0.85 microg/mL vs 2.01 +/- 0.32 microg/mL respectively, P < 0.01), and lower in LPS + Lianshu group than in LPS + berberine group (48.59 +/- 4.70 micromol/L vs 51.56 +/- 8.38 micromol/L, 1.43 +/- 0.53 micromol/mL vs 1.81 +/- 0.42 micromol/mL, 4.00 +/- 0.54 microg/mL vs 4.88 +/- 0.77 microg/mL respectively, P < 0.05). The morphology of the intestinal mucosa showed destroyed villi in LPS group and atrophied intestinal mucosa in other groups. The pathological intestinal mucosal changes were less in LPS + Lianshu group than in LPS group. The number of IgA+ plasma cells and amount of SIgA were higher in LPS + Lianshu group than in LPS group (1.16 +/- 0.19/microm(2) vs 1.09 +/- 0.28/microm(2), P = 0.026; 0.59 +/- 0.12 mg/L vs 0.15 +/- 0.19 mg/L respectively, P = 0.000). Lianshu had counteractive effects on yeast-induced pyrexia and enterokinesia in rats. CONCLUSION: Lianshu preparation has therapeutic effects on LPS-induced diarrhea and enterokinesia in rats.

[Clinical study on pneumoconiosis with pulmonary thromboembolism].

OBJECTIVE: To probe into the clinical features and the rescue of pneumoconiosis with pulmonary thromboembolism (PTE). METHODS: 26 patients with pneumoconiosis and PTE, male 16, female 10, were collected from June 2002 to June 2006 and 42 patients only with pneumoconiosis served as control. Tissue plasminogen activator (t-PA), plasminogen activator inhibitor-1 (PAI-1), thrombomodulin (TM), plasma protein S, C (Ps, Pc), homocysteine (Hcy) were measured by the methods of ILISA, and antithrombin (AT-III) by chromo substrate method before and after the treatment of heparin. RESULTS: The average age of patients with pneumoconiosis and PTE was 66.0 +/- 11.9 years old. The number of patients with pneumoconiosis of degree 1, 2, 3 was 3, 16 and 7 respectively. After anticoagulant therapy of heparin, 23 were well improved, and 3 died of acute respiratory failure. Dyspnea, chest pain, hemoptysis, syncope were the conspicuous symptoms. The levels of D-Dimer (0.63 +/- 0.14 mg/L), TM (5.02 +/- 1.24 microg/L) were significantly higher than those of the control (P < 0.05), and significantly lower again after the treatment (P < 0.05). The level of AT-III (96.68 +/- 7.23%) was significantly lower than that of the control, and higher again after the treatment (P < 0.05). CONCLUSION: PTE is often developed in the elder patients with high degree of pneumoconiosis (> or = 2 degree). Clinical features are complicated and non-specific, with the high negative ratio of D-Dimer (7/26), high mortality and high complications of anticoagulant therapy.