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1.
Kadiombo Anastasie Tshilela Hidekazu Ikeuchi Takayuki Matsumoto Takashi Kuroiwa Noriyuki Sakurai Toru Sakairi Yoriaki Kaneko Akito Maeshima Keiju Hiromura Yoshihisa Nojima 《Clinical and experimental nephrology》2016,20(1):23-29
Background
Aberrant expression of T helper cell (Th) cytokines is believed to play a central role in the pathogenesis of systemic lupus erythematosus (SLE). While the glomerulus is one of the major targets of lupus inflammation, little is known about the cytokine expression in glomeruli. The current study aimed to explore the profiles of Th cytokine gene expressions in isolated glomeruli of lupus-prone mice.Methods
Glomeruli were purified from lupus-prone MRL/lpr mice using the magnetic microbead method. Expressions of cytokine genes representing the Th subset and FoxP3 were examined using real-time polymerase chain reaction. Serum levels of these cytokines were also measured by enzyme-linked immunosorbent assay. MRL/n mice were used as controls. Histologic glomerular damages were scored semiquantitatively. To examine the role of TNF-α in glomerular damage, we administered etanercept, a TNF-α antagonist, into the subjects.Results
Glomerular gene expressions of TNF-α in lpr mice increased with week postpartum and reached statistically significant levels at 16 weeks compared with those of the glomeruli from control mice. Expressions of IFN-γ, IL-4 and FoxP3 also increased, but the difference was not significant. There was a significant increase in serum levels of TNF-α, IFN-γ, and IL-17 and decrease in those of IL-4. Among the genes examined, TNF-α significantly correlated with glomerular damage score. Administration of etanercept did not affect glomerular cytokine expressions or proteinuria and failed to ameliorate histologic glomerular damages.Conclusion
Our data suggest that Th1 cytokines, especially TNF-α, are dominantly expressed in the glomeruli of lupus-prone mice, but its pathophysiological role remains unclear.2.
Brij B. Agarwal Juhil D. Nanavati Nayan Agarwal Naveen Sharma Krishna A. Agarwal Kumar Manish Satish Saluja Sneh Agarwal 《Surgical endoscopy》2016,30(5):1733-1741
Objective
Use of surgical energy is integral to laparoscopic surgery (LS). Energized dissection (ED) has a potential to impact the biomolecular expression of inflammation due to ED-induced collateral inflammation. We did this triple-blind randomized controlled (RCT) study to assess this biomolecular footprint in an index LS, i.e., laparoscopic cholecystectomy (LC).Methods and procedures
This RCT was conducted in collaboration with tertiary-level institutions, from January 2014 to December 2014 with institutional review board clearance. Consecutive, unselected, consenting candidates for LC were randomized (after anesthesia induction) into group I (ED) and group II (non-ED). They were managed with compliance to universal protocols for ethics, informed consent, anesthesia, drug usage and clinical pathway with blinded observers. Biomolecular inflammatory markers, i.e., interleukin 6 (IL-6), tumor necrosis factor-alpha (TNF-α) and highly sensitive CRP (HS-CRP), were measured with blood drawn juxta-preoperatively (H0), at 4 h (H4) and at 24 h (H24). The quantitative changes induced by ED on IL-6, TNF-α and HS-CRP at H0, H4 and H24 with their kinetic behavior were the study endpoint. Prospective data were analyzed statistically with a p value of <0.05 being significant.Results
Two cases from the ED group had biliary injury and hence were withdrawn from analysis. The ED (n = 49) and non-ED (n = 51) groups had similar demographic, clinical and H0 biomolecular variables. There was a significant increase in IL-6, TNF-α and HS-CRP from H0 to H4 in both the groups (p values <0.001). From H4 to H24, all three cytokines showed significant increase in ED group (p < 0.05), whereas in the non-ED group, IL-6 showed significant fall (p = 0.004) and TNF-α showed no significant change (p = 0.063). Both the groups showed H4–H24 elevation of HS-CRP (p = 0.000).Conclusion
Energized dissection adds to the cytokine-mediated postoperative inflammation. The additional ED-induced inflammation can be measured objectively by IL-6 and TNF-α levels.Clinical trials registry
Clinical Trials Registry, India (REF/2014/06/007153).3.
Zhen-Yu Li Yuan-Pei Zhang Jie Zhang Su-Bo Zhang Dai Li Zhen-Zhen Huang Wen-Jun Xin 《Journal of anesthesia》2016,30(1):55-63
Purpose
Bortezomib (BTZ), a widely used chemotherapeutic drug, is closely associated with the development of painful peripheral neuropathy, but the mechanism underlying the induction of this disorder by BTZ remains largely unclear. To examine this association, we have evaluated the activation of mitogen-activated protein kinase (MAPK) family members in the spinal dorsal horn and the role of tumor necrosis factor alpha (TNF-α) and interleukin-1 beta (IL-1β) in BTZ-induced allodynia in rats.Methods
Male Sprague–Dawley rats were used as the model animals. The paw withdrawal test, in which mechanical stimuli (von Frey hairs) is applied to the plantar surface of the hindpaw, was used to determine any changes in the paw withdrawal threshold of the treated rats. A PE-10 catheter was placed intrathecally to deliver TNF-α neutralizing antibody, IL-1 receptor antagonist (IL-1ra) or the c-Jun N-terminal kinase (JNK) inhibitor SP600125. The mRNA levels of various cytokines were measured by real-time quantitative PCR. The expression of TNF-α, IL-1β and mitogen-activated protein kinase (MAPK) family members in the spinal dorsal horn was measured by western blot analysis and immunohistochemistry. All data were expressed as the mean ± standard error of the mean and analyzed using the SPSS version 13.0 software program.Results
The BTZ treatment induced an upsurge in the mRNA and protein levels of TNF-α in the neurons and IL-1β in the astrocytes in the spinal dorsal horn. It also significantly upregulated the phosphorylation of JNK but not of extracellular signal-regulated kinases (ERK) and p38-MAPK in astrocytes of the spinal dorsal horn. Inhibition of TNF-α or IL-1β ameliorated JNK activation and mechanical allodynia induced by BTZ. Co-administration of thalidomide (TNF-α synthesis inhibitor) and IL-1ra prevented BTZ-induced mechanical allodynia.Conclusion
Our results suggest that the TNF-α or IL-1β/JNK pathway in the spinal dorsal horn may play a critical role in the development of painful peripheral neuropathy induced by BTZ.4.
Background
Benign and malignant pathologies of the pancreas can result in a relevant chronic disease burden. This is aggravated by morbidities resulting from surgical resections as well as from progression of the underlying condition.Objective
The aim was to summarize the current evidence regarding epidemiology, pathophysiology, diagnosis and treatment of endocrine and exocrine pancreatic insufficiency, as well as of pancreatic pseudocysts.Material and methods
A selective literature search was performed and a summary of the currently available data on the surgical sequelae after pancreatic resection is given.Results
Reduction of healthy pancreatic parenchyma down to 10–15?% leads to exocrine insufficiency with malabsorption and gastrointestinal complaints. Orally substituted pancreatic enzymes are the therapy of choice. Loss of pancreatic islets and/or islet function leads to endocrine insufficiency and pancreoprivic diabetes mellitus. Inflammatory, traumatic and iatrogenic injuries of the pancreas can lead to pancreatic pseudocysts, which require endoscopic, interventional or surgical drainage if symptomatic. Finally, pancreatic surgery harbors the long-term risk of gastrointestinal anastomotic ulcers, bile duct stenosis, portal vein thrombosis and chronic pain syndrome.Conclusion
As the evidence is limited, an interdisciplinary and individually tailored approach for delayed pancreatic morbidity is recommended.5.
Ulrich C. Liener Mario Perl Markus S. Huber-Lang Daniel H. Seitz Uwe B. Brückner Florian Gebhard Markus W. Knöferl 《Langenbeck's archives of surgery / Deutsche Gesellschaft fur Chirurgie》2011,396(2):251-259
Purpose
The purpose of this study was to characterize the local pulmonary inflammatory environment and to elucidate alterations of alveolar macrophage (AMØ) functions after blunt chest trauma.Methods
Wistar rats were subjected to blunt chest trauma. AMØ were isolated, stimulated, and cultured. Bronchoalveolar lavage (BAL) was collected. Cytokines/chemokines were quantified in the BAL and in AMØ supernatants via ELISA. AMØ phagocytic and chemotactic activity and respiratory burst capacity were assessed.Results
Following chest trauma, a significant increase of IL-1β (at 6 and 24 h) and IL-6 (at 24 h) in BAL was observed, whereas IL-10 and TNF-α concentrations were not altered. MIP-2 and CINC were substantially increased as early as 6 h and PGE2 early at 10 min, whereas BAL MCP-1 was not elevated until 24 h after trauma. MIP-2 release by AMØ isolated form trauma animals was markedly increased as early as 10 min after injury. IL-1β and IL-10 exhibited a late increase at 24 h. AMØ TNF-α release was increased at 6 h. At 6 or 24 h, AMØ from trauma animals incorporated significantly more opsonized latex beads than their sham controls, and their chemotactic activity was substantially enhanced at 24 h. AMØ oxidative burst capacity remained largely unchanged.Conclusions
Already very early after chest trauma, inflammatory mediators are present in the intraalveolar compartment. Additionally, AMØ are primed to release cytokines and chemokines. Blunt chest trauma also changes the phagocytic and chemotactic activity of AMØ. These functional changes of AMØ might enable them to better ward off potential pathogens in the course after trauma.6.
Purpose
Pancreas-sparing duodenectomy (PSD) represents an alternative procedure to pancreatoduodenectomy (PD) for patients with duodenal neoplasms.Methods
The postoperative early and late complications of 21 patients who underwent PSD between 1992 and 2014 were compared with those of 44 patients with soft pancreatic parenchyma who underwent PD between 2009 and 2014.Results
The median operation time and blood loss were less in the PSD group than in the PD group (P < 0.001). The overall incidence of early complications was less in the PSD group than in the PD group (PSD with ampullectomy vs. PSD without ampullectomy vs. PD; 45.5 vs. 20.0 vs. 56.8 %). The incidence of pancreatic fistula formation and overall incidence of late complications were also less in the PSD group than in the PD group (P = 0.031, 0.020). There were no complications related to the pancreatic endocrine or exocrine functions in the PSD group.Conclusion
PSD is a less-invasive procedure and has the advantage over PD of preserving the pancreas.7.
Jiazheng Li Nobuhisa Kandatsu Guo-Gang Feng Jia-Zhen Jiang Lei Huang Hiroyuki Kinoshita Shoshiro Okada Yoshihiro Fujiwara 《Journal of anesthesia》2016,30(3):420-426
Purpose
The present study, conducted in rats, investigated whether propofol attenuates lipopolysaccharide (LPS)-triggered liver dysfunction via regulation of tumor necrosis factor (TNF)-α production in activated Kupffer cells.Methods
Rats received LPS (500 μg/kg) under Urethane? sedation (1 g/kg) in combination with propofol (5 mg/kg/h) or Intralipid? from 1 h before to 6 h after LPS administration. Some rats were treated with 10 mg/kg gadolinium chloride (GdCl3) to induce Kupffer cell depletion. The serum levels of alanine aminotransferase (ALT) and aspartate aminotransferase (AST), TNF-α mRNA and protein expression, caspase-3 activation and apoptosis were evaluated in hepatocytes. Immunofluorescence staining revealed expression of the pan-macrophage marker CD68 as well as TNF-α in Kupffer cells.Results
ALT and AST serum levels increased approximately four-fold in LPS-exposed rats compared with Intralipid?-treated rats at 6 h after LPS administration, whereas propofol and GdCl3 reduced the LPS-induced increases. LPS simultaneously augmented TNF-α expression in Kupffer cells, followed by increased caspase-3 activity and apoptosis in hepatocytes. Immunofluorescence staining and immunoblotting assay showed that TNF-α expression in Kupffer cells was inhibited by propofol and GdCl3, resulting in a reduction of caspase-3 activity and apoptosis in LPS-treated rat hepatocytes.Conclusions
Propofol (5 mg/kg/h) attenuated LPS-triggered liver dysfunction via inhibition of TNF-α production in activated Kupffer cells. These results suggest that propofol is capable of inhibiting inflammation-induced liver dysfunction in vivo.8.
Bertrand Le Roy Johan Gagnière Pascal Chabrot Denis Pezet Armand Abergel Emmanuel Buc 《Journal of gastrointestinal surgery》2016,20(9):1671-1672
Background
Transjugular intrahepatic portosystemic shunt (TIPS) is the standard procedure in the treatment of refractory ascites and variceal bleeding in the setting of portal hypertension. Secondary obstruction of the shunt is a classic but potentially lethal complication.Methods
We present here the case of a cirrhotic patient that underwent a TIPS for refractory ascites, with early complete thrombosis without lethal complication.Results
Obstruction of the TIPS led to thrombosis of both the right hepatic and the right portal veins with progressive total atrophy of the right liver and marked hypertrophy of the left liver. Despite initial poor liver function, biological hepatic markers improved slowly until complete recovery.Conclusion
Hence, we suggest the concept of combined right portal and hepatic vein embolization as a new procedure to induce partial liver hypertrophy before major liver resection, even in cirrhotic patients.9.
X. Wu X. Feng Y. He Y. Gao S. Yang Z. Shao C. Yang H. Wang Z. Ye 《Osteoporosis international》2016,27(5):1827-1837
Summary
Macrophages play an important role during the development of steroid-induced osteonecrosis. Interleukin (IL)-4 administration helped reduce the infiltration of M1 phenotypic macrophages and maintain the activation of M2 phenotypic macrophages, resulting in restriction of inflammation and decrease in osteocyte apoptosis. The results indicated the therapeutic potential of IL-4 in prevention of steroid-induced osteonecrosis.Introduction
Steroid-induced osteonecrosis (ON) is a debilitating disease characterized by the activation and infiltration of macrophages into the necrotic site. This study aimed to investigate the effects of IL-4 administration on macrophage polarization and the involved signaling pathways.Methods
Fifty-six BALB/c mice were randomly divided into two groups, group M (model group) and group MI (treatment group), each containing 28 mice. ON model was induced by the injection of methylprednisolone (MPS). The mice in group MI received intra-abdominal injections of 2 μg/100 g/day of rIL-4 for five consecutive days, following the administration of MPS. Osteonecrosis was verified by histopathological staining. The expression of tumor necrosis factor-alpha (TNF-α) was analyzed by ELISA and immunohistochemistry. The infiltration of M1/M2 macrophages was examined by the expression of specific makers of F4/80, CD11c, and CD206 protein. Cell apoptosis was detected by terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL) assay, and the apoptotic signal molecules such as STAT1 and caspase-3 were examined.Results
Histopathological observations indicated that IL-4 administration reduced the incidence of ON and the accumulation of osteoclasts. IL-4 administration inhibited the expression of TNF-α and reduced the infiltration of M1 phenotypic macrophages and maintained relatively high level of M2 phenotypic macrophages. Additionally, TUNEL assay suggested that IL-4 intervention could reduce the number of apoptotic cells in the necrotic zone. The anti-apoptotic mechanisms were related to STAT1 phosphorylation and the activation of caspase-3.Conclusions
Il-4 administration could alleviate steroid associated ON in mice by inhibiting the inflammatory response, the infiltration of M1 phenotypic macrophages, and suppressing TNF-a-induced osteocytic apoptosis by inhibiting the STAT1-caspase-3 signal pathway.10.
Purpose
Prophylactic abdominal drainage is performed routinely after liver resection in many centers. The aim of this study was to examine the safety and validity of liver resection without abdominal drainage and to clarify whether routine abdominal drainage after liver resection is necessary.Methods
Patients who underwent elective liver resection without bilio-enteric anastomosis between July, 2006 and June, 2012 were divided into two groups, based on whether surgery was performed before or after, we adopted the no-drain strategy. The “former group” comprised 256 patients operated on between July, 2006 and June, 2009 and the “latter group” comprised 218 patients operated between July, 2009 and June, 2012. We compared the postoperative complications, percutaneous drainage, and postoperative hospital stay between the groups, retrospectively.Results
There were no significant differences in the rates of postoperative bleeding, intraabdominal infection, or bile leakage between the groups. Drain insertion after liver resection did not reduce the rate of percutaneous drainage. Postoperative hospital stay was significantly shorter in the latter group.Conclusion
Routine abdominal drainage is unnecessary after liver resection without bilio-enteric anastomosis.11.
María Victoria Alvarez-Sánchez O. B. Luna I. Oria K. Marchut F. Fumex G. Singier A. Salgado B. Napoléon 《Journal of gastrointestinal surgery》2018,22(7):1213-1220
Background
It has been suggested that EUS-BD may be a feasible and safer alternative to percutaneous transhepatic biliary drainage (PTBD) after failed ERCP in patients with ascites. To date, no study has specifically evaluated the performance of EUS-BD in this context.Methods
Retrospective analysis was done for patients with and without ascites who underwent EUS-BD for malignant biliary obstruction after failed ERCP between July 2010 and September 2014. Complications and technical and clinical successes between the two groups were compared.Results
A total of 31 patients were included: 20 patients without ascites (group 1) and 11 with ascites (group 2). Nineteen patients underwent EUS-hepaticogastrostomy (six in group 2), and 12 underwent EUS-choledochoduodenostomy (five in group 2). Technical success was achieved in all patients. Clinical success was observed in 95% (n?=?19) in group 1 and 64% (n?=?7) in group 2 (p?=?0.042). In three out of four patients without clinical success in group 2, the follow-up period was not long enough to observe the clinical response because of early death within the 2 weeks after EUS-BD secondary to disease progression or preprocedural unresponsive sepsis. No significant differences were observed between groups 1 and 2 either in the overall rates of procedural-related complications (20 and 9%, respectively, p?=?0.63) or in the rates of major complications (15 vs 9%, respectively, p?=?0.639). Stent migration occurred in one patient in each group, intra- or post-procedural bleeding occurred in two patients in group 1, which was conservatively managed, and one patient in group 1 presented biliary leakage. Stent patency and the number of re-interventions were not significantly different.Conclusions
EUS-BD is technically feasible in patients with ascites. Our results suggest that EUS-BD may be a clinically effective and safe alternative after failed ERCP in patients with ascites.12.
Background
Curcumin exhibits anti-inflammatory effects and has been suggested as a treatment for inflammatory diseases. The aim of this study was to investigate the effects of curcumin on the lipopolysaccharide induced inflammatory response in rat gingival fibroblasts in vitro and ligation-induced experimental periodontitis in vivo, and to speculate the possible anti-inflammatory mechanism of curcumin.Methods
The gingival fibroblasts were incubated with different concentrations of curcumin in the absence or presence of lipopolysaccharide (LPS). Concentrations of interleukin-1β(IL-1β), tumor necrosis factor-α (TNF-α), osteoprotegerin (OPG) and soluble receptor activator of nuclear factor kappa-B ligand (RANKL) culture supernatants of rat gingival fibroblasts were determined by enzyme linked immunosorbent assay. The nuclear fraction of rat gingival fibroblasts was extracted and nuclear factor kappa-B (NF-κB) activation was assessed by western blotting to elucidate related mechanisms. Curcumin was given every two days by oral gavage. The gingival inflammation and alveolar bone loss between the first and second molars were observed by hematoxylin and eosin staining. Collagen fibers were observed by picro-sirius red staining. Alveolar bone loss was assessed by micro-CT analysis.Results
Curcumin attenuated the production of IL-1β and TNF-α in rat gingival fibroblasts stimulated by LPS, and inhibited the LPS-induced decrease in OPG/sRANKL ratio and NF-κB activation. Curcumin significantly reduced gingival inflammation and modulated collagen fiber and alveolar bone loss in vivo.Conclusions
curcumin modulates inflammatory activity in rat periodontitis by inhibiting NF-κB activation and decreasing the OPG/sRANKL ratio induced by LPS.13.
Objective
For evaluation of a novel surgical procedure for the treatment of chylous ascites.Summary background data
Chylous ascites is a debilitating condition associated with high morbidity and mortality rates. At least one-third of patients are refractory to medical therapy and may warrant further treatment. Traditional methods involving ligation of lymphatic fistulas or small bowel resection do not address the basic pathophysiologic mechanism of the underlying obstruction, and identification of chyloperitoneal fistulas may be challenging.Methods
A novel flap based on deep inferior epigastric vessels with its surrounding lymphatic fatty tissue was designed in this study and transferred into abdominal cavity, with anastomosis to the fourth jejunal vessels. Three consecutive cases with chylous ascites treated by this vascularized lymphatic cable transfer were retrospectively reviewed.Results
All three patients recovered from chylous ascites after the lymphatic cable transfer and tolerated regular diet well, with follow-up of 3 years at least.Conclusions
Lymphatic cable flap based on the deep inferior epigastric vessels could be a potential option for treatment of intractable chylous ascites, with safe and successful long-term outcomes in three consecutive patients. The proposed functional mechanism of the flap is bypass of the obstructed intra-abdominal lymphatics to an extraperitoneal route as well as local lymphangiogenesis.14.
Santos AC Lima EM Penido MG Silveira KD Teixeira MM Oliveira EA Simões E Silva AC 《Pediatric nephrology (Berlin, Germany)》2012,27(6):941-948
Background
Recent studies suggest that cytokines modulate bone turnover. Idiopathic hypercalciuria (IH) seems to be associated with bone mineral loss. Therefore, the aim of this study was to assess cytokines involved in bone turnover in patients with IH.Methods
Plasma and spot-urine levels of interleukin (IL)-1β, IL-6, IL-8, tumor necrosis factor alpha (TNF-α), transforming growth factor β1 (TGF-β1), and monocyte chemoattractant protein (MCP-1) were measured in 70 children and adolescents with IH and in 37 healthy controls. Patients with IH were subdivided according to their calciuria at the time of sample collection: ≥4 mg/kg/day (persistent IH, n=27) and below 4 mg/kg/day (controlled IH, n=43). Cytokines were determined by enzyme-linked immunoassay.Results
Plasma and urinary concentrations of IL-1β, IL-6, IL-8, and TNF-α were undetectable in all groups. No differences were found between controlled and persistent hypercalciuria for plasma and urinary levels of MCP-1 and TGF-β1. On the other hand, MCP-1 levels were significantly higher in both subgroups of IH in comparison to healthy controls. Furthermore, urinary MCP-1 levels of IH patients correlated positively with bone mineral content (p=0.013).Conclusion
Although cytokine measurements did not allow the differentiation between persistent and controlled IH, our findings suggest that MCP-1 might play a role in patients with IH.15.
S. Alonso M. Donat L. Carrion J. M. Rodriguez L. Diego D. Acin A. Serrano E. Perez F. Pereira 《Hernia》2016,20(4):531-533
Purpose
Patients with cirrhosis and ascites are prone to abdominal wall complications largely predominate by umbilical hernia. Elective surgery is indicated in select patients but a high morbidity and mortality rate occurs if it is performed in emergency conditions.Methods
We present a clinical case of a patient with advanced alcoholic liver disease who came to the emergency room for an acutely incarcerated umbilical hernia. Due to the high surgical risk, we had to discuss other treatment options.Results
The use of umbilical paracentesis for incarcerated hernia reduction in cirrhotic patients with tense ascites is a safe and reproducible technique.Conclusions
Umbilical paracentesis could be considered as an alternative to emergency surgery in these high-risk patients.16.
Introduction
Laparoscopic and robotic surgery of the pancreas has only recently emerged as viable treatment options for benign and malignant disease. This review seeks to evaluate the current body of evidence on these approaches to pancreaticoduodenectomy and distal pancreatectomy.Methods
A systematic review of large published series was performed utilizing the PubMed search engine.Results
Based on these reports, both the laparoscopic and robotic techniques for these complex procedures appear to be safe and effective, if performed by high volume experienced pancreatic surgeons. The advantages of each approach are highlighted, emphasizing the data available on the learning curve and potential dissemination.Conclusions
Both minimally invasive approaches to pancreatic resection are safe and feasible.17.
Ide T Kitajima Y Miyoshi A Ohtsuka T Mitsuno M Ohtaka K Miyazaki K 《Annals of surgical oncology》2007,14(9):2600-2607
Background
Pancreatic cancer is one of the representative solid tumors, in which the hypoxic microenvironment plays a crucial role in malignant progression. We previously demonstrated that tumor-stromal interaction under hypoxia enhances the invasiveness of pancreatic cancer cells through hepatocyte growth factor (HGF)/c-Met signaling.Methods
We investigated the immunohistochemical expression of hypoxia inducible factor-1α (HIF-1α) c-Met, and HGF in both cancer and stromal cells using 41 pancreatic cancer tissue specimens, and tried to identify any correlations with the clinical features and survival.Results
Positive staining for HIF-1α was observed in both pancreatic cancer and the surrounding stromal cells in more than 30% of the cases, and it significantly correlated with lymph node metastasis (P < .05). A significant correlation was observed between the expression of HIF-1α and HGF in stromal cells (P < .05). In addition, the c-Met expression in cancer cells was found to significantly correlate with the HGF expression in not only cancer but also stromal cells. The disease-free survival rates of the patients with HIF-1α in cancer, stromal, c-Met in cancer, and an HGF expression in stromal cells was significantly worse than those without such expressions (P < .05).Conclusions
These data suggest that the HGF/c-Met signaling via HIF-1α ?may therefore negatively affect the prognosis in patients with pancreatic cancer, and targeting tumor stroma under hypoxia might thus be potentially useful as a novel therapy for this cancer.18.
P.?Srikanth R.?F.?Chun M.?Hewison J.?S.?Adams R.?Bouillon D.?Vanderschueren N.?Lane P.?M.?Cawthon T.?Dam E.?Barrett-Connor L.?B.?Daniels J.?M.?Shikany M.?L.?Stefanick J.?A.?Cauley E.?S.?Orwoll C.?M.?Nielson for the Osteoporotic Fractures in Men Study Research Group 《Osteoporosis international》2016,27(7):2291-2300
Summary
Vitamin D is hypothesized to suppress inflammation. We tested total and free vitamin D metabolites and their association with inflammatory markers. Interleukin-6 levels were lower with higher 25-hydroxyvitamin D. 1,25-dihydroxyvitamin D and free 25OHD associations mirrored those of 25OHD. However, associations for the two metabolites diverged for tumor necrosis factor alpha (TNF-α) soluble receptors.Introduction
Vitamin D is hypothesized to suppress inflammation, and circulating 25-hydroxyvitamin D (25OHD) and inflammatory markers are inversely correlated. However, total serum 25OHD may not be the best indicator of biologically active vitamin D.Methods
We tested serum total 25OHD, total 1,25(OH)2D, vitamin D binding protein (DBP), and estimated free 25OHD and free 1,25(OH)2D associations with inflammatory markers serum interleukin-6 (IL-6), TNF-α and their soluble receptors, interleukin-10 (IL-10), and C-reactive protein (CRP) as continuous outcomes and the presence of ≥2 inflammatory markers in the highest quartile as a dichotomous outcome, in a random subcohort of 679 men in the Osteoporotic Fractures in Men (MrOS) study.Results
IL-6 was lower in men with higher 25OHD (?0.23 μg/mL per standard deviation (SD) increase in 25OHD, 95 % confidence intervals (CI) ?0.07 to ?0.38 μg/mL) and with higher 1,25(OH)2D (?0.20 μg/mL, 95 % CI ?0.0004 to ?0.39 μg/mL); free D associations were slightly stronger. 25OHD and DBP, but not 1,25(OH)2D, were independently associated with IL-6. TNF-α soluble receptors were inversely associated with 1,25(OH)2D but positively associated with 25OHD, and each had independent effects. The strongest association with ≥2 inflammatory markers in the highest quartile was for free 1,25(OH)2D (odds ratios (OR) 0.70, 95 % CI 0.54 to 0.89 per SD increase in free 1,25(OH)2D).Conclusions
Associations of 1,25(OH)2D and free 25OHD with IL-6 mirrored those of 25OHD, suggesting that 1,25(OH)2D and free D do not improve upon 25OHD in population-based IL-6 studies. However, associations for the two metabolites diverged for TNF-α soluble receptor, warranting examination of both metabolites in studies of TNF-α and its antagonists.19.
Purpose
We previously reported that TU-100 suppresses irinotecan hydrochloride (CPT-11)-induced inflammatory cytokines and apoptosis. However, the mechanism underlying this effect has not been fully elucidated. The aim of this study was to further clarify the mechanism of CPT-11-induced bacterial translocation (BT) and the effect of TU-100 on BT.Methods
Cell cytotoxicity was assessed in vitro by a WST-8 assay. For the in vivo experiments, rats were randomly divided into 3 groups: the control group, the CPT-11 group (250 mg/kg i.p. for 2 days), and the CPT-11 and TU-100 co-treated group (1000 mg/kg, p.o. for 5 days). All of the rats were sacrificed on day 6 and their tissues were collected.Results
CPT-11 and TU-100 co-treatment improved CPT-11 the related cytotoxicity in vitro. All CPT-11-treated rats developed different grades of diarrhea and BT was observed in 80% of the rats. CPT-11 caused a significant increase in the expression of TLR4, IL-6, TNF-α, IL-1β and caspase-3 mRNAs in the large intestine. The expression of tight junction (TJ) marker mRNAs (occludin, claudin-1 and 4, and ZO-1) was significantly decreased in comparison to the control group. TU-100 co-treatment significantly reversed diarrhea, BT, and the expression of TLR2, IL-6, TNF-α, IL-1β and caspase-3, and improved the expression of occludin, claudin-4 and ZO-1.Conclusions
TU-100 can suppress the adverse effects associated with CPT-11 and improve the function of the TJ. It is possible that this occurs through the TLR pathway.20.