Synergistic Effect of Co3(HPO4)2(OH)2 Cocatalyst and Al2O3 Passivation Layer on BiVO4 Photoanode for Enhanced Photoelectrochemical Water Oxidation.

Bismuth vanadate (BVO) is regarded as an exceptional photoanode material for photoelectrochemical (PEC) water splitting, but it is restricted by the severe photocorrosion and slow water oxidation kinetics. Herein, a synergistic strategy combined with a Co3(HPO4)2(OH)2 (CoPH) cocatalyst and an Al2O3 (ALO) passivation layer was proposed for enhanced PEC performance. The CoPH/ALO/BVO photoanode exhibits an impressive photocurrent density of 4.9 mA cm-2 at 1.23 VRHE and an applied bias photon-to-current efficiency (ABPE) of 1.47% at 0.76 VRHE. This outstanding PEC performance can be ascribed to the suppressed surface charge recombination, facilitated interfacial charge transfer, and accelerated water oxidation kinetics with the introduction of the CoPH cocatalyst and ALO passivation layer. This work provides a novel and synergistic approach to design an efficient and stable photoanode for PEC applications by combining an oxygen evolution cocatalyst and a passivation layer.

SPEN induces miR-4652-3p to target HIPK2 in nasopharyngeal carcinoma.

SPEN family transcriptional repressor (SPEN), also known as the SMART/HDAC1-associated repressor protein (SHARP), has been reported to modulate the malignant phenotypes of breast cancer, colon cancer, and ovarian cancer. However, its role and the detail molecular basis in nasopharyngeal carcinoma (NPC) remain elusive. In this study, the SPEN mRNA and protein expression was found to be increased in NPC cells and tissues compared with nonmalignant nasopharyngeal epithelial cells and tissues. Elevated SPEN protein expression was found to promote the pathogenesis of NPC and lead to poor prognosis. Knockdown of SPEN expression resulted in inactivation ofPI3K/AKT and c-JUN signaling, thereby suppressing NPC migration and invasion. In addition, miR-4652-3p was found to be a downstream inducer of SPEN by targeting the homeodomain interacting protein kinase 2 (HIPK2) gene, a potential tumor suppressor that reduces the activation of epithelial-mesenchymal transition (EMT) signaling, thereby reducing its expression and leading to increased NPC migration, invasion, and metastasis. In addition, SPEN was found to induce miR-4652-3p expression by activating PI3K/AKT/c-JUN signaling to target HIPK2. Our data provided a new molecular mechanism for SPEN as a metastasis promoter through activation of PI3K/AKT signaling, thereby stimulating the c-JUN/miR-4652-3p axis to target HIPK2 in NPC.

EIF3H interacts with PDCD4 enhancing lung adenocarcinoma cell metastasis.

Lung adenocarcinoma (LUAD) is a common type of lung cancer characterized by a high incidence of local invasion and metastasis. Programmed cell death factor 4 (PDCD4) is a well-recognized tumor suppressor gene involved in LUAD, however its precise regulatory mechanism remains elusive. This is the first study to report an inverse regulatory relationship between PDCD4 and eukaryotic translation initiation factor 3 subunit H (EIF3H) in LUAD. Co-immunoprecipitation assays combined with mass spectrometry and immunofluorescent co-localization indicated that PDCD4 interacted with EIF3H. Overexpression of PDCD4 in LUAD cells reduced EIF3H mRNA and protein levels by suppressing c-Jun-induced EIF3H transcription. Further, an elevated level of EIF3H protein was found in LUAD tissues compared with para-cancerous normal lung tissues, and was found to be an unfavorable factor promoting LUAD pathogenesis. Moreover, the negative correlation between PDCD4 and EIF3H protein expression was confirmed in LUAD tissues. Functional analyses showed that EIF3H overexpression promoted LUAD cell migration and invasion in vitro as well as metastasis in nude mice by activating epithelial-mesenchymal transition (EMT) signaling. Conversely, EIF3H knockdown with small interfering RNAs reversed these changes in LUAD cells. Furthermore, we discovered that introduction of PDCD4 to EIF3H-overexpressing LUAD cells abrogated the function of EIF3H, reducing migration and invasion of LUAD cells by downregulating EMT signaling. Taken together, our findings identified a previously unknown negative regulation of PDCD4 on EIF3H and confirmed EIF3H as an oncogenic factor in LUAD by enhancing EMT signaling, which was abrogated by PDCD4.

[Characteristic analysis of plasma lipid metabolism level in patients with colorectal adenoma].

OBJECTIVE: To evaluate the relationship between serum lipid level and colorectal adenoma. METHODS: A review analysis was carried out of the patients who underwent colonoscopy in Peking University Third Hospital from May 2009 to February 2010. Subjects with history of colorectal adenocarcinoma before colorectal surgery or of medication which had influenced the serum lipid level were excluded. Adenoma group included the patients who had colorectal adenoma which was evidenced by pathology. The patients with no adenoma were ascribed to control group. The serum total cholesterol, triglyceride, HDL cholesterol and LDL cholesterol levels of the two groups were analyzed. The relation between serum lipid level and location of colorectal adenoma was also summarized. RESULTS: A total of 227 patients were included for final analysis, of whom 124 were in adenoma group (77 males and 47 females; mean age: 56.5±10.7 years )and 103 in control group(53 males and 50 females; mean age: 56.8±13.6 years). Serum triglyceride level in adenoma group [(1.83±1.04) mmol/L] was significantly higher than that of control group[(1.54±0.86) mmol/L(P=0.022)] and HDL-C level in adenoma group[(1.05±0.32) mmol / L] was significantly lower than that of control group [(1.26±0.46) mmol/L(P=0.000)]. In adenoma group, 73 cases were with HDL-C decreased, which was significantly higher than that of control group (44 cases, P=0.015). In addition, higher incidence of proximal colonic adenomas was observed in elevated triglycerides group and low HDL-C group (39.8%, 37.4%), compared with control group (25.5%), but there was no statistical difference between the two groups(P=0.358). CONCLUSION: The findings of this study suggest that dyslipidemia may affect the incidence of colorectal adenoma, particularly hypertriglyceridemia and low HDL-C levels. In addition, higher triglyceride and lower HDL-C levels seem to be related to higher incidence of proximal colonic adenomas.

[Role of peroxisome proliferators-activated receptor-gamma in the chemical prevention therapy of sulindac for precancerous lesions of rats].

OBJECTIVE: To understand whether peroxisome proliferators-activated receptor-gamma (PPAR-gamma) plays an important role in the chemopreventive effect of sulindac on precancerous lesions (aberrant crypt foci, ACF) of rats. METHODS: Male Sprague-Dawley rats were used in this study and raised in Special Pathogen Free room. Sulindac was the main research object. Carcinogenic agent, 1, 2-dimethylhydrazine (DMH), was used to induce colonic precancerous lesions. Pioglitazone was chosen as agonist of PPAR-gamma and GW9662 used as a specific complete antagonist of PPAR-gamma. ACFs were induced according to the protocol certified in prior experiments. There were 7 groups, named as Negative control group, DMH group, Sulindac group, Sulindac+GW9662 group, Pioglitazone group, Pioglitazone+GW9662 group and GW9662 group. The experiment period was 12 weeks. At the end of the experiment, all rats were sacrificed by euthanasia. Half of the colon including the rectum was taken and immersed in formalin at 4 degrees Celsius overnight, and then recorded the number and size of ACF with the help of anatomic microscope stained by methylene blue. RESULTS: (1) Sulindac and agonist of PPAR-gamma could significantly inhibit DMH-induced ACFs of rats from 137.8+/-59.4 to 73.9+/-32.1 and 96.4+/-32.6 with a decrease of 45.7% (P<0.01) and 30.0%(P<0.05) compared with DMH group. Antagonist of PPAR-gamma could counteract the chemopreventive effect of sulindac with an increase from 73.9+/-32.1 to 106.3+/-33.9; (2) The expression of PPAR-gamma in colorectal mucosa increased significantly during the DMH induction period compared with negative control group, the relative values of gray were 0.304+/-0.288 and 2.292+/-1.380 (P<0.01), sulindac and pioglitazone could decrease the expression of PPAR-gamma remarkably compared with DMH group, the relative values of gray were 1.023+/-1.115 and 0.352+/-0.187 (P<0.01), and the application of GW9662, antagonist of PPAR-gamma could promote the expression of PPAR-gamma in some degree, and the relative values of gray were 1.279+/-0.303 and 0.998+/-0.295 (P>0.05). CONCLUSION: The expression of PPAR-gamma had risen in DMH-induced ACFs of rats significantly. Sulindac and agonist of PPAR-Gamma (pioglitazone) could inhibit the formation of ACF, and followed by a decrease of PPAR-gamma. Antagonist of PPAR-gamma could interfere with the effect of sulindac. PPAR-gamma might play an important role in the chemopreventive effect of sulindac on colorectal pre-cancerous lesions of rats and activation of PPAR-gamma pathway could inhibit the initiation and evolvement of ACF induced by DMH.

[Effect of peroxisome proliferators-activated receptor-gamma in the mechanisms of sulindac against large intestine carcinoma].

OBJECTIVE: To compare effects of sulindac, PPARgamma activator and PPARgamma antagonist on the proliferation and apoptosis of the colonic cancer cells, and to investigate whether sulindac exerts its colonic neoplasm inhibiting activity through pathway of PPARgamma. METHODS: Cell strain HT-29 of colonic cancer was divided into six groups: the control group, sulindac group, 15d-PGJ2 (PPARgamma activator) group, GW9662 (PPARgamma antagonist) group, sulindac+GW9662 group and 15d-PGJ2+ GW9662 group. After 24 and 48 hours' culturing, proliferation status of each group was determined by immunocytochemical staining of PCNA, and cell apoptosis status was determined by double staining method of AnnexinV-FITC/PI, examined on flow cytometer. RESULTS: (1) Proliferation status of the colonic cancer cells of each group: 24 and 48 hours after medication, PCNA positive ratios were 33.2%+/- 4.5% and 25.0%+/-4.7% of the control group, 11.8%+/-3.7% and 8.6%+/-1.9% of sulindac group, 11.2%+/-2.5% and 11.4%+/-2.1% of 15d-PGJ2 group, 35.3%+/-4.3% and 26.8%+/-3.9% of GW9662 group, 16.5%+/-5.3% and 12.2 %+/-2.4% of sulindac + GW9662 group, 21.0%+/-4.8% and 21.5%+/-4.2% of 15d-PGJ2+GW9662 group. (2) Apoptosis ratio of colonic cancer cells of each group: 24 hours after medication, apoptosis rate of colonic cancer cells was 13.0%+/-1.0% of the control group, 41.0%+/-2.6% of sulindac group, 11.5%+/-0.6% of 15d-PGJ2 group, 12.4%+/-0.9% of GW9662 group,33.6%+/-2.3% of sulindac+GW9662 group, and 13.0%+/-1.0% of 15d-PGJ2 + GW9662 group. 48 hours after medication, apoptosis rate was 14.0%+/-3.4% of the control group, 95.3%+/-1.5% of sulindac group, 31.5%+/-2.3% of 15d-PGJ2 group, 13.0%+/-1.9% of GW9662 group, 86.8%+/-0.4% of sulindac+GW9662 group, and 12.9%+/-1.0% of 15d-PGJ2+GW9662 group. CONCLUSION: Both sulindac and PPARgamma activator can inhibit proliferation and promote apoptosis of colonic cancer cells, and their effects can be antagonized by PPARgamma antagonist, which indicates that as a kind of PPARgamma ligand, sulindac can inhibit proliferation of colonic cancer cells via activating PPARgamma.

[Current diagnostic status, clinical and pathologic manifestation for a Crohn's disease].

OBJECTIVE: To evaluate the contemporary diagnostic and therapeutic status for Crohn's disease (CD), and analyze its clinical and pathologic manifestation. METHODS: Retrospectively we reviewed 220 hospitalized inflammatory bowel disease (IBD) cases in which 48 were diagnosed as CD. Data of diagnostic and therapeutic details were recorded. RESULTS: In the past 10 years 44 of the 48 CD cases were diagnosed in recent and 75.0% of the cases were in the onset age range from 17 to 40 years. The most common symptoms were abdominal pain, diarrhea and bloody stool. 16 (33.3%) of the cases were accompanied with extra-intestinal manifestations, 3 (6.3%) with perianal abscess, and 2 (4.2%) with intestinal fistulation. The main findings through colonoscopy were ulceration, obstruction and cobble stone sign, with a diagnostic correspondence of 85.7% (36/42). Non-caseous granulomas were totally identified in 43.2% (19/44) of the histology. Thirty cases were administrated with Sulfasalazine/Mesalazine (SASP/5-ASA) or corticosteroids/immuno-suppressor in which 27 got clinically improved. Thirteen patients underwent surgery. CONCLUSION: The diagnostic incidence of Crohn's disease has been increased in recent years. The combination of endoscopy, radiography and histology is the best way for the diagnosis of CD. Small intestinal endoscopy and capsule endoscopy with repeated histopathology and follow-up are helpful for the diagnosis.

[The effects of sulindac on the pathology of colorectal remnant polyps of familial adenomatous polyposis (FAP) patients].

OBJECTIVE: To evaluate the long-term effectiveness of sulindac on the pathology of colorectal adenomas of familial adenomatous polyposis (FAP) patients. METHODS: FAP patients were treated with sulindac 400 mg per day. The change of colorectal polyps was assessed every 3 months in the first year. After the significant regression of colorectal polyps was achieved, sulindac was used to maintain the effects. The patients received colonoscopy examination regularly. Biopsies of remnant polyps and other lesions were obtained. The type and dysplasia grade of biopsies were evaluated and compared with baseline. RESULTS: Before the study, 90.8% of adenoma biopsies were tubular, while 9.2% was tubulovillous adenoma. The dysplasia of grades I, II and III were 42.1%, 45.6% and 12.3%, respectively. After sulindac treatment, 99.8% of adenoma biopsies were tubular, while 0.2% tubulovillous adenoma. There was significant difference compared with baseline (P<0.01). The dysplasia of grades I, II and III were 55.8%, 41.8% and 2.4% respectively, which had significant difference with baseline (P<0.01). Minor flat elevation and erythema were found during the treatment, in which approximately 65% was adenoma. CONCLUSION: Long-term use of sulindac seems to be effective in reducing dysplasia grade and tubulovillous adenoma of retained colorectal adenoma of FAP patients. Minor flat elevation and erythema may be the lesions appearing during the regression of adenoma.

[Pioglitazone, a peroxisome proliferators-activated receptor gamma ligand, inhibits dimethylhydrazine (DMH) induced aberrant crypt foci in rats].

OBJECTIVE: To investigate the chemopreventive effects of pioglitazone (exogenous PPAR gamma ligand) on rat colon aberrant crypt foci, a rat carcinogenesis model induced by dimethylhydrazine (DMH), and to compare pioglitazone with sulindac (a NSAID). METHODS: Thirty-two, 8-week-old, female Sprague-Dawley rats were randomly divided into four groups (n = 8 each). Group 1 rats were injected with DMH alone (120 mg.kg-1, single subcutaneous injection). Group 2 rats were injected with saline alone. Group 3 rats were pre-treated with sulindac (320 mg.kg-1) for 7 days before DMH initiation. Group 4 rats were treated with pioglitazone (100 mg.kg-1). The animals were killed at the end of the experiment (week 5) and the colons were stained with methylene blue. The aberrant crypt foci (ACF) of the colonic mucosa were assessed. RESULTS: In Group 1 rats (DMH only), the average numbers of ACF/colon and AC/colon were (182 +/- 93) and (263 +/- 198), respectively. In Group 2 (saline group) rats, no ACF were found. In Group 3 (sulindac group) rats, the average numbers of ACF/colon and AC/colon were (91 +/- 49) and (140 +/- 69), respectively. Both of them were decreased significantly compared with the values in Group 1 (P < 0.01 and P < 0.05). In Group 4 (pioglitazone group) rats, the average numbers of ACF/colon and AC/colon were (97 +/- 23) and (148 +/- 31), respectively. Both of them were decreased significantly compared with the values in Group 1 (P < 0.01 and P < 0.05). No difference was found in the values of Group 3 and Group 4. CONCLUSION: These results suggest that pioglitazone have chemopreventive effects against rat colon carcinogenesis induced by DMH, whose effect is similar to that of sulindac.