Kaempferide ameliorates cisplatin-induced nephrotoxicity via inhibiting oxidative stress and inducing autophagy.

Acute kidney injury (AKI) caused by anti-tumor drugs, such as cisplatin, is a severe complication with no effective treatment currently, leading to the reduction or discontinuation of chemotherapy. Natural products or herbal medicines are gradually considered as promising agents against cisplatin-induced AKI with the advantages of multi-targeting, multi-effects, and less resistance. In this study, we investigated the effects of kaempferide, a natural flavonoid extracted from the rhizome of Kaempferia galanga, in experimental AKI models in vitro and in vivo. We first conducted pharmacokinetic study in mice and found a relative stable state of kaempferide with a small amount of conversion into kaempferol. We showed that both kaempferide (10 µM) and kaempferol (10 µM) significantly inhibited cisplatin-caused injuries in immortalized proximal tubule epithelial cell line HK-2. In AKI mice induced by injection of a single dose of cisplatin (15 mg/kg), oral administration of kaempferide (50 mg/kg) either before or after cisplatin injection markedly improved renal function, and ameliorated renal tissue damage. We demonstrated that kaempferide inhibited oxidative stress and induced autophagy in cisplatin-treated mice and HK-2 cells, thus increasing tubular cell viability and decreasing immune responses to attenuate the disease progression. In addition, treatment with kaempferide significantly ameliorated ischemia-reperfusion-induced renal injury in vitro and in vivo. We conclude that kaempferide is a promising natural product for treating various AKI. This study has great implications for promotion of its use in healthcare products, and help to break through the limited use of cisplatin in the clinic.

[Cordyceps sinensis combined with Jujing Pills for male infertility].

OBJECTIVE: To observe the clinical effect and safety of Cordyceps sinensis (CS) combined with Jujing Pills (JJP) in the treatment of male infertility. METHODS: We randomly divided 90 male infertility patients into three groups of an equal number and treated them with JJP tid 5g once, CS bid 1g once and CS+JJP, respectively, all for 12 weeks. Before and after 4, 8 and 12 weeks of medication, we obtained the semen volume, sperm concentration, percentages of progressively motile sperm (PMS) and morphologically normal sperm (MNS) and sperm DNA fragmentation index (DFI), and compared them between the two groups of patients. RESULTS: The total therapeutic effectiveness rate was significantly higher in the CS+JJP than in the CS and JJP groups (96.42% vs 78.57% and 63.33%, P < 0.05), and so was PMS (ï¼»30.05 ± 10.24ï¼½% vs ï¼»24.74 ± 11.24ï¼½% and ï¼»22.71 ± 13.60ï¼½%, P < 0.01). The CS+JJP group also showed a higher percentage of MNS than the JJP group (ï¼»4.16 ± 2.86ï¼½% vs ï¼»2.73 ± 1.86ï¼½%, P < 0.01) but lower than the CS group (ï¼»5.03 ± 2.99ï¼½%) (P < 0.05). The sperm DFI was markedly lower in the CS+JJP than in the CS and JJP groups (ï¼»15.26 ± 6.93ï¼½% vs ï¼»15.90 ± 7.39ï¼½% and ï¼»16.85 ± 8.52ï¼½%, P < 0.05). CONCLUSIONS: Cordyceps sinensis combined with Jujing Pills can effectively improve sperm quality and reduce sperm DFI. Based on the TCM theory of "mutual generation between metal and water", Cordyceps sinensis can significantly enhance the effectiveness of the kidney-tonifying therapy.

[Associations between the efficiency of the brain white matter network and clinical symptoms in patients with type â ¢ B prostatitis].

OBJECTIVE: To investigate the changes in the topological properties of the global and local nodal efficiencies of the brain white matter network in patients with type III B prostatitis, and to analyze the correlation between the information transmission efficiency of different brain regions and pelvic pain. METHODS: We enrolled 19 patients with type Ⅲ B prostatitis and 32 normal controls matched in general demographic data for this study. We assessed the pelvic pain of the patients based on the NIH-CPSI, obtained the structural and diffusion-weighted MR images of the brain, preprocessed the MRI data, constructed the brain structural networks and calculated the topological properties of the nodal local and global efficiencies using the FSL software package and brain connection toolbox. Finally, we compared the topological properties between the two groups by t-test with the SPSS 20 software, performed multiple correction of the values using the false discovery rate (FDR) method, and investigated the associations of the altered brain regions with the NIH-CPSI scores by Pearson correlation analysis. RESULTS: The global efficiency of the orbital part of the right median frontal gyrus in the patients with type Ⅲ B prostatitis, compared with that in the normal controls, was dramatically decreased (0.095 ± 0.046 vs 0.13 ± 0.015, P < 0.01) while that of the left median cingulate gyrus markedly increased (0.16 ± 0.027 vs 0.14 ± 0.019, P < 0.01), which were corrected by FDR. The local efficiency of the left median cingulate gyrus was also remarkably decreased in the patients as compared with that in the controls (0.25 ± 0.075 vs 0.19 ± 0.036, P < 0.01), and so was that of the left paracentral lobule (0.25 ± 0.088 vs 0.17 ± 0.065, P < 0.01), which were corrected by FDR. In the patients, the local efficiencies of the left precuneus (r = 0.46, P = 0.045), right supplementary motor area (r = 0.47, P = 0.043) and left median cingulate gyrus (r = 0.60, P = 0.0065) were positively correlated with the total score of NIH-CPSI, the scores of pain and discomfort symptoms, and the scores of the influence of the symptoms on the quality of life. CONCLUSIONS: The changes of the brain regions in the executive control network of the patient with type Ⅲ B prostatitis might be involved in enhancing his sensitivity to pain and discomfort, and consequently lead to pelvic pain and discomfort.

An Analysis Regarding the Association Between DAZ Interacting Zinc Finger Protein 1 (DZIP1) and Colorectal Cancer (CRC).

Colorectal cancer (CRC) is the third most common malignant disease worldwide, and its incidence is increasing, but the molecular mechanisms of this disease are highly heterogeneous and still far from being fully understood. Increasing evidence suggests that fibrosis mediated by abnormal activation of fibroblasts based in the microenvironment is associated with a poor prognosis. However, the function and pathogenic mechanisms of fibroblasts in CRC remain unclear. Here, combining scrna-seq and clinical specimen data, DAZ Interacting Protein 1 (DZIP1) was found to be expressed on fibroblasts and cancer cells and positively correlated with stromal deposition. Importantly, pseudotime-series analysis showed that DZIP1 levels were up-regulated in malignant transformation of fibroblasts and experimentally confirmed that DZIP1 modulates activation of fibroblasts and promotes epithelial-mesenchymal transition (EMT) in tumor cells. Further studies showed that DZIP1 expressed by tumor cells also has a driving effect on EMT and contributes to the recruitment of more fibroblasts. A similar phenomenon was observed in xenografted nude mice. And it was confirmed in xenograft mice that downregulation of DZIP1 expression significantly delayed tumor formation and reduced tumor size in CRC cells. Taken together, our findings suggested that DZIP1 was a regulator of the CRC mesenchymal phenotype. The revelation of targeting DZIP1 provides a new avenue for CRC therapy.

Lumican expression in pancreatic ductal adenocarcinoma.

BACKGROUND/AIMS: The present study was aimed to investigate lumican expression in and correlation with severity of pancreatic ductal adenocarcinoma (PDA). METHODOLOGY: We assessed mRNA expression and protein localization (using immunohistochemistry) in PDA samples collected from 260 patients. Additionally, we compared lumican expression with expression of Ki-67, VEGF and mutated p53 proteins, which are markers of cancer progression. RESULTS: Expression levels of lumican mRNA and protein in cancer tissue were significantly higher than those in tumor-adjacent tissue (t=5.69, p<0.05). The stromal expression of lumican in poorly differentiated cases was significantly higher at stage T4 than stage T2-3 (χ²=21.06, p<0.05); similarly, the stromal expression of lumican was significantly higher in TNM stage III-IV than in stage I-Il (χ²=17.01, p<0.05). Additionally, expression of Ki67 was higher in poorly differentiated cases than in highly-moderately differentiated cases (χ²=13.06, p<0.05). Finally, in highly-moderately differentiated samples, stromal expression of lumican was negatively correlated with expression of Ki-67, VEGF and mutated P53 (p<0.05). CONCLUSIONS: Lumican expression is higher in pancreatic ductal adenocarcinoma than in tumor-adjacent tissue, and the correlation of lumican expression with TNM stage in poorly differentiated samples, in contrast with its negative correlation with expression of Ki-67, VEGF and mutated P53 mutation in highly-moderately differentiated samples.

Melatonin inhibits the expression of vascular endothelial growth factor in pancreatic cancer cells.

OBJECTIVE: To investigate the effects of melatonin on cellular proliferation and endogenous vascular endothelial growth factor (VEGF) expression in pancreatic carcinoma cells (PANC-1). METHODS: PANC-1 cells were cultured for this study. The secreted VEGF concentration in the culture medium was determined using ELISA method, VEGF production in the tumor cells was detected by immunocytochemistry, and VEGF mRNA expression was determined by RT-PCR. RESULTS: Higher melatonin concentrations significantly inhibited cellular proliferation, with 1 mmol/L concentration exhibiting the highest inhibitory effect (P<0.01). VEGF concentrations in the cell culture supernatants and intra-cellules were all significantly reduced after melatonin (1 mmol/L) incubation (P<0.05). VEGF mRNA expression decreased markedly in a time-dependent manner during the observation period (P<0.05). CONCLUSIONS: High melatonin concentrations markedly inhibited the proliferation of pancreatic carcinoma cells. The endogenous VEGF expression was also suppressed by melatonin incubation.

Prognostic Significance of CCDC137 Expression and Its Association with Immune Infiltration in Hepatocellular Carcinoma.

Globally, hepatocellular carcinoma (HCC) is one of the most common causes of cancer-associated mortalities. The clinical outcome of HCC patients remains poor due to distant metastasis and recurrence. In recent years, growing evidences have confirmed that the coiled-coil domain-containing (CCDC) family proteins are involved in the progression of several diseases. However, the expression and clinical significance of the coiled-coil domain-containing 137 (CCDC137) in hepatocellular carcinoma (HCC) have not been investigated. Level 3 mRNA expression profiles and clinicopathological data were obtained in TCGA-LIHC. Differentially expressed genes (DEGs) were screened between 371 HCC and 50 nontumor specimens. The prognostic value of CCDC137 was analyzed in HCC patients. The correlations between CCDC137 and cancer immune infiltrates were investigated. In this study, a total of 2897 DEGs were obtained: 2451 genes were significantly upregulated and 446 genes were significantly downregulated. KEGG assays revealed that these DEGs were involved in tumor progression. Among 2897 DEGs, we found that CCDC137 expression was distinctly increased in HCC specimens compared with nontumor specimens. A high level of CCDC137 expression was related to an advanced tumor stage and grade. Moreover, patients with higher levels of CCDC137 expression had a shorter overall survival and disease-free survival than patients with lower CCDC137 levels. CCDC137 expression was positively correlated with infiltrating levels of several immune cells, such as CD8 T cells and Th2 cells. Finally, in vitro experiments confirmed that CCDC137 expression was highly expressed in HCC cells, and its knockdown suppressed the proliferation of HCC cells. Taken together, our findings revealed that CCDC137 might be used as a biomarker for immune infiltration and poor prognosis in HCC, which offered fresh insight on potential therapies for HCC.

Overexpression of SLC25A51 promotes hepatocellular carcinoma progression by driving aerobic glycolysis through activation of SIRT5.

Solute carrier family 25 member 20 (SLC25A51) is a newly identified mammalian mitochondrial NAD+ transporter. However, the clinicopathological and biological significance of SLC25A51 in human cancers, including hepatocellular carcinoma (HCC), remains unclear. The aim of this study was to define the role of SLC25A51 in HCC progression. Here we demonstrate that SLC25A51 is significantly overexpressed in human HCC specimens and cell lines, caused by, at least in partial, the decrease of miR-212-3p. SLC25A51 overexpression is positively correlated with the clinicopathological characteristics of vascular invasion and tumor diameter, as well as poor survival in patients with HCC. Knockdown of SLC25A51 attenuated, while overexpression of SLC25A51 enhanced the growth and metastasis of HCC cells both in vitro and in vivo. Mechanistically, glucose metabolism reprogramming from oxidative phosphorylation to glycolysis by activation of mitochondrial sirtuin 5 (SIRT5) was found to contribute to the promotion of growth and metastasis by SLC25A51 in HCC cells. Together, these findings reveal important roles of SLC25A51 in HCC tumorigenesis and suggest SLC25A51 as a promising prognostic marker and therapeutic target for treating HCC.

Polyphosphate binds to the principal sigma factor of RNA polymerase during starvation response in Helicobacter pylori.

Helicobacter pylori persists deep in the human gastric mucus layer in a harsh, nutrient-poor environment. Survival under these conditions depends on the ability of this human pathogen to invoke starvation/stress responses when needed. Unlike many bacteria, H. pylori lacks starvation/stress-responding alternative sigma factors, suggesting an additional mechanism might have evolved in this bacterium. Helicobacter pylori produces polyphosphate; however, the role and target of polyphosphate during starvation/stress have not been identified. Here we show that polyphosphate accumulated during nutrient starvation directly targets transcriptional machinery by binding to the principal sigma factor in H. pylori, uncovering a novel mechanism in microbial stress response. A positively charged Lys-rich region at the N-terminal domain of the major sigma factor is identified as the binding region for polyphosphate (region P) in vivo and in vitro, revealing a new element in sigma 70 family proteins. This interaction is biologically significant because mutant strains defective in the interaction undergo premature cell death during starvation. We suggested that polyphosphate is a second messenger employed by H. pylori to mediate gene expression during starvation/stress. The putative 'region P' is present in sigma factors of other human pathogens, suggesting that the uncovered interaction might be a general strategy employed by other pathogens.

[The role of apoptosis in the stress-related changes of intestinal mucosa barrier following traumatic brain injury].

OBJECTIVE: To investigate the role of epithelial cell apoptosis in the stress-related changes of intestinal mucosa barrier following traumatic brain injury. METHODS: Sixty-four health male Wistar rats were divided randomly into two groups: (1) traumatic brain injury model group (n = 32), in which rats suffered from traumatic brain injury by Feeney's method; (2) control group (n = 32), rats suffered from sham operation. Each group were divided into four subgroups according 6 h, 12 h, 24 h, and 48 h after operation (n = 8, for each subgroup). Ileum tissue were taken to observed the damage of the intestinal mucosa under microscope and electron microscope. The early apoptosis rate of intestinal mucosal cells were analyzed with Annexin V-PI double stained and detected by flow cytometry. RESULTS: The intestinal mucosa were damaged and the intercellular space of intestinal mucosal were found increased in traumatic brain injury group. The early apoptosis rate of intestinal mucosal epithelial cells was significant increased in traumatic brain injury group than that in control group [6 h: (13.5 ± 3.7)% vs (6.1 ± 1.7)%, P < 0.05; 12 h: (66.1 ± 6.0)% vs (5.2 ± 1.1)%, P < 0.05; 24 h: (39.8 ± 4.8)% vs (8.4 ± 2.6)%, P < 0.05; 48 h: (7.5 ± 1.3)% vs (6.6 ± 0.5)%]. CONCLUSION: The increased early apoptosis rate of intestinal mucosal epithelial cells might contribute to the stress-damage of the intestinal mucosa barrier in early stage of traumatic brain injury.

[Effect of oxygen free radicals on bacterial translocation in rats with traumatic brain injury].

OBJECTIVE: To investigate the effect of oxygen free radicals on intestinal mucosal barrier in traumatic brain injury rats. METHODS: A total of 64 health male Wistar rats were divided randomly into two groups: traumatic brain injury (TBI) (n=32); Control group with sham operation (n=32). Each group was divided into four subgroups at 6, 12, 24 and 48 h post-operation (n=8). The levels of malondialdehyde (MDA), superoxide dismutase (SOD) and glutathione (GSH) were measured in intestinal mucosa, mesenteric lymph nodes, liver, spleen, pancreas, lung and kidney tissue. The marked bacilli were counted under a fluorescent microscope. RESULTS: The positive rates of bacterial translocation in TBI group were obviously higher than those of control group (6 h: 8.3% vs. 2.1%, 12 h: 25.0% vs. 2.1%, 24 h: 27.1% vs. 2.1%, 48 h: 12.5% vs. 0.0% , P < 0.05). The levels of MDA in TBI group were obviously higher than those of control group (6 h: 4.9 +/- 0.7 vs. 2.6 +/- 0.3, 12 h: 6.1 +/- 0.8 vs. 2.8 +/- 0.5, 24 h: 5.9 +/- 0.4 vs. 2.6 +/- 0.3, 48 h: 5.3 +/- 0.5 vs. 2.7 +/- 0.4 (nmol/mg pro), P < 0.05), and GSH (6 h: 287 +/- 36 vs. 408 +/- 253; 12 h: 192 +/- 25 vs. 421 +/- 46; 24 h: 160 +/- 48 vs. 432 +/- 35; 48 h: 241 +/- 31 vs. 394 +/- 51 (mg/g pro) P < 0.05). SOD (6 h: 19.5 +/- 3.3 vs. 21.1 +/- 1.9; 12 h: 11.8 +/- 2.6 vs. 20.7 +/- 5.3; 24 h: 13.3 +/- 3.3 vs. 20 +/- 3.3; 48 h: 15.1 +/- 1.5 vs. 21.2 +/- 3.2 (U/mg pro). P < 0.05) were lower than the control group at the same time point. CONCLUSIONS: Bacterial translocation occurs obviously in TBI rats. It indicates that oxygen free radicals play important roles in stress-related changes of intestinal mucosal barrier in early stage of traumatic brain injury.

[Effect of esomeprazole upon intestinal mucosal damage following traumatic brain injury in rats].

OBJECTIVE: To explore the protective effect of esomeprazole upon stress-related intestinal mucosal damage following traumatic brain injury (TBI) in rats. METHODS: Male Wistar rats were randomly divided into three groups: groups A and B served as TBI models and group C was designated as a normal control (shame operation). In group B rats were treated subcutaneously with esomeprazole prior to TBI while groups A and C rats were treated with an equivalent amount of normal saline. During the observation period, the morphological changes of brain tissue and intestinal mucosa were observed. And the intestinal mucosal permeability to fluorescein isothiocyanate (FITC)-labeled dextran and diamine oxidase (DAO) activity were assessed. The activities of superoxide dismutase (SOD), myeloperoxidase (MPO) and the levels of malondialdehyde (MDA), reduced glutathione (GSH) and hydroxyl radical (OH(*)) were measured. RESULTS: (1) During the observation period of TBI, the intestinal mucosal was damaged, but there was improvement in group PPI. (2) FITC-dextran leakage increased after TBI and peaked at 24 h (P < 0.01); its level of (3720 +/- 401) ng/ml in group PPI was lower than that in group TBI (5230 +/- 489) ng/ml (P < 0.05). (3) The DAO activity in mucosa decreased and the decline was the greatest at 24 h (P < 0.05), its level of (0.44 +/- 0.11) ng/ml in group PPI at 24 h was higher than that in group TBI (0.31 +/- 0.07) ng/ml (P < 0.05); while the DAO activity in serum increased significantly. (4) The activity of SOD and the level of GSH in intestinal mucosal started to decrease at 3 h and the decline was the greatest at 24 h (P < 0.05), their levels were (10.2 +/- 2.8) U/mgprot and (140 +/- 46) mg/gprot respectively in group TBI, a remarkable drop in comparison with those of PPI group (13.0 +/- 2.4) U/mgprot and (208 +/- 48) U/gprot (P < 0.05). (5) The levels of OH(.), MDA and MPO in intestinal mucosal increased and peaked at 24 h (P < 0.05), the respective levels in group PPI (108 +/- 8), (6.2 +/- 0.6) and (1.53 +/- 0.52) U/mgprot and those in the TBI group (150 +/- 8), (7.7 +/- 0.9), (1.93 +/- 0.53) U/mgprot, demonstrated that there was a remarkable rise (P < 0.05). CONCLUSION: Traumatic brain injury may lead to stress-related intestinal mucosal damage. Oxygen free radicals play an important role in intestinal mucosal barrier damage. Esomeprazole attenuates the damage of intestinal mucosal barrier by antioxidant effect and inhibiting the activity of neutrophil.

Modified human uterus transplantation using ovarian veins for venous drainage: the first report of surgically successful robotic-assisted uterus procurement and follow-up for 12 months.

OBJECTIVE: To report the 12-month results of the first human uterus transplantation case using robot-assisted uterine retrieval. This type of transplantation may become a treatment for permanent uterine factor infertility. DESIGN: Case study. SETTING: University hospital. PATIENT(S): A 22-year-old woman with complete müllerian agenesis who underwent a previous surgery for vaginal reconstruction. The live uterine donor was her mother. INTERVENTION(S): The uterus transplantation procedure consisted of robot-assisted uterine procurement, orthotopic replacement and fixation of the retrieved uterus, revascularization, and end-to-side anastomoses of bilateral hypogastric arteries and ovarian-uterine vein to the bilateral external iliac arteries and veins. MAIN OUTCOME MEASURE(S): Data from preoperative investigations, surgery, and follow-up (12 months). RESULT(S): The duration of the donor and recipient surgeries were 6 and 8 hours, 50 minutes, respectively. No immediate perioperative complications occurred in the recipient or donor. The recipient experienced menarche 40 days after transplant surgery, and she has had 12 menstrual cycles since the surgery. No rejection episodes occurred in the recipient. CONCLUSION(S): These results demonstrate the feasibility of live-donor uterine transplantation with a low-dose immunosuppressive protocol and the role of DaVinci robotic assistance during human uterine procurement. CLINICAL TRIAL REGISTRATION NUMBER: XJZT12Z06.

[Study on the cholelitholytic effect and safety of the preparation of Chinese medicine compound].

OBJECTIVE: To study the cholelitholytic effect and safety of the preparation of Chinese medicine compound. METHOD: Experiments were performed to study the efficacy of gallstones dissolution of the preparation of Chinese medicine compound in vitro and in vivo. The toxicity was studied by pathological and blood biochemical changes. RESULT: The preparation of Chinese medicine compound dissolved cholesterol and mixing gallstones in 7 days in vitro and in vivo, no influence on the blood biochemistry and the other organs of the rabbits. CONCLUSION: The preparation of Chinese medicine compound is effective and safe for treatment of chololithiasis.

Pig Liver Xenotransplantation: A Review of Progress Toward the Clinic.

Experience with clinical liver xenotransplantation has largely involved the transplantation of livers from nonhuman primates. Experience with pig livers has been scarce. This brief review will be restricted to assessing the potential therapeutic impact of pig liver xenotransplantation in acute liver failure and the remaining barriers that currently do not justify clinical trials. A relatively new surgical technique of heterotopic pig liver xenotransplantation is described that might play a role in bridging a patient with acute liver failure until either the native liver recovers or a suitable liver allograft is obtained. Other topics discussed include the possible mechanisms for the development of the thrombocytopenis that rapidly occurs after pig liver xenotransplantation in a primate, the impact of pig complement on graft injury, the potential infectious risks, and potential physiologic incompatibilities between pig and human. There is cautious optimism that all of these problems can be overcome by judicious genetic manipulation of the pig. If liver graft survival could be achieved in the absence of thrombocytopenia or rejection for a period of even a few days, there may be a role for pig liver transplantation as a bridge to allotransplantation in carefully selected patients.

Blocking Notch signal in myeloid cells alleviates hepatic ischemia reperfusion injury by repressing the activation of NF-κB through CYLD.

Ischemia-reperfusion (I/R) is a major reason of hepatocyte injury during liver surgery and transplantation. Myeloid cells including macrophages and neutrophils play important roles in sustained tissue inflammation and damage, but the mechanisms regulating myeloid cells activity have been elusive. In this study, we investigate the role of Notch signaling in myeloid cells during hepatic I/R injury by using a mouse model of myeloid specific conditional knockout of RBP-J. Myeloid-specific RBP-J deletion alleviated hepatic I/R injury. RBP-J deletion in myeloid cells decreased hepatocytes apoptosis after hepatic I/R injury. Furthermore, myeloid-specific RBP-J deletion led to attenuated inflammation response in liver after I/R injury. Consistently, Notch blockade reduced the production of inflammatory cytokines by macrophages in vitro. We also found that blocking Notch signaling reduced NF-κB activation and increased cylindromatosis (CYLD) expression and knockdown of CYLD rescued reduction of inflammatory cytokines induced by Notch blockade in macrophages during I/R injury in vitro. On the other hand, activation of Notch signaling in macrophages led to increased inflammatory cytokine production and NF-κB activation and decreased CYLD expression in vitro. These data suggest that activation of Notch signaling in myeloid cells aggravates I/R injury, by enhancing the inflammation response by NF-κB through down regulation of CYLD.

Diagnostic value of bone-specific alkaline phosphatase in lung carcinoma patients with bone metastases: a meta-analysis.

UNLABELLED: Aim and Backgrounds: The accurate diagnosis of lung carcinoma patients with bone metastases is crucial for therapy and the prevention of complications. We performed a systematic review and meta-analysis to evaluate the diagnostic value of serum bone-specific alkaline phosphatase (BALP) in lung carcinoma patients with bone metastases. METHODS: Such databases as PubMed, Embase, Cochrane Library, Web of Science, Ovid, BioMed Central, Biosis previews and four Chinese databases (Chinese Biomedical Literature Database-disc (CBM), Chinese National Knowledge Infrastructure (CNKI), Technology of Chongqing (VIP) and Wan Fang DATA) were retrieved on computer, and the relevant journals were also manually searched to collect the trials on BALP in diagnosis of lung carcinoma patients with bone metastases. The meta-analysis was conducted by using Meta-Disc 1.4 software. RESULTS: A total of 8 studies were included, and there were 848 lung carcinoma patients diagnosed by gold standard, patients were divided into two groups: 419 cases with bone metastases and 429 cases without bone metastases. The meta-analysis showed that, the pooled sensitivity (SEN), specificity (SPE), positive likelihood ratio (PLR), negative likelihood ratio (NLR) and diagnostic odds ratio (DOR) was 0.48 [95% CI (0.43 to 0.53)], 0.86 [95% CI (0.82 to 0.89)], 3.14 [95% CI (2.47 to 3.99)], 0.62 [95% CI (0.56 to 0.68)], 6.66 [95% CI (4.62 to 9.60)] respectively. And the AUC of SROC was 0.78, (Q*=0.72). CONCLUSION: BALP has greater diagnostic value in detecting lung carcinoma patients with bone metastases. However, further large scale studies are required to confirm the predictive value.

[Laboratory and clinical study of levofloxacin against Helicobacter pylori].

OBJECTIVE: To assess antibacterial activity of levofloxacin to Helicobacter pylori (Hp) strains In Vitro and In Vivo. METHODS: The Minimum inhibitory concentration (MIC) for 52 clinical isolates was detected by agar dilution method and was compared with those of amoxicillin and clarithromycin. To examine the effects of pH variation on the susceptibility of Hp to levofloxacin, Mueller-Hinton agar with 7% defibrinated sheep blood was adjusted to a pH range of 4.0, 5.0, 7.0 by adding hydrochloric acid. 85 Hp-positive Patients with chronic active gastritis or active peptic ulcer disease were consecutively recruited in a prospective, open-label study. The enrolled patients were randomised to receive a seven-day course of omeprazole 20 mg bid plus amoxicillin 1000mg bid and levofloxacin 200mg bid. Their Hp status was assessed by (13)C-urea breath test and/or endoscopy 4 - 6 weeks after the end of treatment. RESULTS: The resistant rates of strains to levofloxacin, amoxicillin and clarithromycin were 1.9%, 11.5% and 25%, respectively. A dual-resistance to amoxicillin and clarithromycin was demonstrated in five Hp strains (9.6%), which were all susceptible to levofloxacin. The prevalence of strains with resistance to levofloxacin was lower than that of strains with resistance to clarithromycin (P < 0.01), and was no statistically different with amoxicillin (P > 0.05). The activity of levofloxacin was diminished under acidic environment (P < 0.01). 84 enrolled patients completed the study. 76 patients (PP and ITT analysis, 91.7%; 90.6%) become Hp-negative. Slight side-effects occurred in 5 patients (5.9%). CONCLUSION: In the present study, we report a high rate of resistance to amoxicillin and clarithromycin in this region. Omeprazole/levofloxacin-based triple therapy, including amoxicillin, is attractive because they combine a high eradication efficacy with an excellent tolerability and safety profile.

Curcumin regulates hepatoma cell proliferation and apoptosis through the Notch signaling pathway.

Curcumin has become a compound of interest for its antioxidant and anti-neoplastic properties. This study sought to determine the effect of curcumin administration on cell proliferation and apoptosis in hepatoma cells. SMMC-7721 hepatoma cells were treated with 10, 30, or 90 µM curcumin solution, with DMEM alone (negative control), or with 20 mg/L fluorouracil (positive control). MTT colorimetry detected significant differences in the rates of cell proliferation inhibition following curcumin treatment, with increasing inhibition accompanying increasing doses of curcumin (P < 0.05), compared to the negative control. Similarly, flow cytometry revealed significant differences in the numbers of apoptotic cells following curcumin treatment: increasing doses of curcumin produced increases in the numbers of apoptotic cells (P < 0.05). To determine whether curcumin exerts these effects by altering the Notch signaling pathway, a phenomenon reported for other cancers, relative expression of Notch1 mRNA and protein were determined in curcumin-treated cells. Both mRNA and protein expression of Notch1 decreased with increasing curcumin dose (P < 0.05). Thus, curcumin appears to inhibit proliferation and induce apoptosis in hepatoma cells by altering the Notch signaling pathway.