CDK12 Promotes the Proliferation, Migration, and Angiogenesis of Gastric Carcinoma via Activating the PI3K/AKT/mTOR Signaling Pathway.

Cyclin-dependent kinase 12 (CDK12) has been found to regulate tumor progression. However, its function in gastric carcinoma (GC) remains controversial. This work aimed to explore the exact effect of CDK12 on GC progression. We detected the expression of CDK12 in GC cells and normal gastric mucosal epithelial cells. Then CDK12 function on GC cell proliferation, migration, and angiogenesis was researched by colony formation experiment, Transwell experiment, and angiogenesis assay. Moreover, CDK12 effect on the PI3K/AKT/mTOR pathway activity was explored by western blot. Further, we used LY294002 (10 µM) to treat GC cells to verify whether CDK12 regulates GC progression by activating the PI3K/AKT/mTOR pathway. Additionally, CDK12 effect on the expression of prognostic factors of GC was detected by western blot, including alkaline phosphatase (ALP) and Ki67. Quantitative real-time polymerase chain reaction and western blot were utilized to evaluate the expression of mRNAs and proteins. As a result, CDK12 was upregulated in GC cells. CDK12 overexpression facilitated the proliferation, migration, and angiogenesis of GC cells. However, CDK12 silencing showed an opposite result. CDK12 overexpression activated the PI3K/AKT/mTOR pathway, but CDK12 silencing inactivated it in GC cells. The blockage of the PI3K/AKT/mTOR pathway induced by LY294002 treatment counteracted the promotion of CDK12 on the proliferation, migration, and angiogenesis of GC. Further, CDK12 silencing suppressed the expression of ALP and Ki67 proteins in GC cells. Taken together, CDK12 promotes the proliferation, migration, and angiogenesis of GC by activating the PI3K/AKT/mTOR pathway. It may be a novel target for GC treatment.

Enhancing the efficiency of planar heterojunction perovskite solar cells via interfacial engineering with 3-aminopropyl trimethoxy silane hydrolysate.

The interfacial compatibility between compact TiO2 and perovskite layers is critical for the performance of planar heterojunction perovskite solar cells (PSCs). A compact TiO2 film employed as an electron-transport layer (ETL) was modified using 3-aminopropyl trimethoxy silane (APMS) hydrolysate. The power conversion efficiency (PCE) of PSCs composed of an APMS-hydrolysate-modified TiO2 layer increased from 13.45 to 15.79%, which was associated with a significant enhancement in the fill factor (FF) from 62.23 to 68.04%. The results indicate that APMS hydrolysate can enhance the wettability of γ-butyrolactone (GBL) on the TiO2 surface, form a perfect CH3NH3PbI3 film, and increase the recombination resistance at the interface. This work demonstrates a simple but efficient method to improve the TiO2/perovskite interface that can be greatly beneficial for developing high-performance PSCs.

Targeting miR-155 suppresses proliferation and induces apoptosis of HL-60 cells by targeting Slug/PUMA signal.

Recent studies have shown that high miR-155 expression was associated with poor prognosis in patients with acute myelogeneous leukemia (AML). Furthermore, targeting miR-155 results in monocytic differentiation and apoptosis. However, the exact role and mechanisms of miR-155 in human AML remains speculative. HL-60 cells were treated with anti-miR-155 for 72 h. Cell growth and apoptosis in vitro were detected by MTT, BrdU proliferation, colony formation and flow cytometry assay. The effect of anti-miR-155 on growth of HL-60 cells was also evaluated in a leukemia mouse model. Slug cDNA and PUMA siRNA trannsfection was used to assess the signal pathway. Different protein expression was detected by western blot assay and quantitative reverse transcriptase polymerase chain reaction (qRT-PCR) assay. The results shown that targeting miR-155 resulted in a 24-fold decrease of miR-155 expression compared to negative control in the HL-60 cells. Targeting miR-155 significantly downregulated Slug and upregulated PUMA expression, and decreased HL-60 cell growth by 70% , impaired colony formation by approximately 60%, and increased HL-60 cell apoptosis by 45%. Targeting PUMA reversed miR-155 sliencing-induced proliferation and apoptosis of HL-60 cells. Restoration of Slug decreased PUMA expression. In murine engraftment models of HL-60 cells, we showed that targeting miR-155 was able to reduce tumor growth. This was accompanied with decreased Slug expression and increased PUMA expression in these tumors. Collectively, our findings strongly suggest targeting miR-155 exhibited in vivo and in vitro antileukemic activities in AML through a novel mechanism resulting in inhibition of Slug expression and increase of PUMA expression.

Hyperthermic intraperitoneal chemotherapy plus high-frequency diathermic therapy followed by intravenous chemotherapy versus intravenous chemotherapy alone for postoperative adjuvant treatment of gastrointestinal cancer: a comparative research study.

PURPOSE: To evaluate the therapeutic efficacy and toxicity of hyperthermic intraperitoneal chemotherapy (HIPEC) plus high-frequency diathermic therapy (HFDT) followed by intravenous chemotherapy vs intravenous chemotherapy alone for adjuvant treatment of postoperative gastrointestinal neoplasms. METHODS: Fifty-two gastrointestinal carcinoma patients who were radically operated were enrolled and divided into the treatment group and the control group. In the treatment group, 25 patients were treated with combination of HIPEC+HFDT and subsequent intravenous chemotherapy, while in the control group 27 patients received intravenous chemotherapy alone. Post-therapeutic complications and adverse reactions, time to progression (TTP) and overall survival (OS) were compared between these two groups. RESULTS: Difference in toxic reactions between the two groups was not statistically significant (p>0.05). Postoperative progression- free survival (PFS) rate at 12 and 40 months after radical surgery was 72.0 and 54.0% respectively in the treatment group, and 65.8 and 11.5% respectively in the control group (p=0.108). TTP was statistically significantly longer in the treatment group than in the control group (median TTP 40.1 vs 18.5 months, p=0.027). Postoperative OS at 12 and 20 months after radical surgery was 88.0 and 78.0% respectively in the treatment group and 92.6 and 72.7% in the control group, without significant difference. CONCLUSION: After radical surgery, combination of HIPEC+HFDT and subsequent intravenous chemotherapy brings about superior PFS compared with intravenous adjuvant chemotherapy alone, while having no more complications and adverse reactions.

[The New Bacteria Expressing Recombinant Multi-epitope Vaccine against Helicobacter pylori and Its Microbiological Characteristics].

OJECTIVE: To construct the engineering bacteria with recombinant plasmid expressing the multi-epitope vaccine which composed of Helicobacter pylori urea membrane channel protein (UreI), Helicobacter pylori urease B subunit (UreB) and cholera toxin B subunit (CTB), and then to study it's microbiological characteristics. METHODS: The sequence contains some dominant epitopes of Helicobacter pylori UreI and UreB was designed, and ctB was added at the N-terminal, all the sequence were linked by flexible linkers. Codon optimization was done according to Escherichia coli (E. coli) BL21 (DE3) bias, the optimized sequence was designated BIB. BIB sequence was synthesized and cloned into plasmid pET28a(+). The recombinant plasmid was confirmed by restriction enzyme digestion and DNA sequencing. The recombinant protein BIB was expressed in E. coli BL21 (DE3) and analyzed by Western blot. RESULTS: The plasmid of pET28a(+)/BIB was constructed successfully, confirmed by restriction enzyme digestion and DNA sequencing. The recombinant protein BIB with relative molecular mass about 33 x 10(3) could be produced by E. coli BL21 (DE3) and was detected by Western blot. The relative molecular mass and N-terminal amino acid sequence of BIB were 100% identity with the design. CONCLUTION: The engineering bacteria with recombinant plasmid expressing the multi-epitope vaccine against Helicobacter pylori was constructed successfully. The recombinant protein BIB can be identified by anti-Sydney strain 1 of Helicobacter pylori (H. pylori SS1) polyclonal antibody and anti-CTB monoclonal antibody, which demonstrated that BIB has the expected antigenicity.

[Improvement of left ventricular hypertrophy by anemic-correcting erythropoietin therapy in chronic renal insufficiency].

OBJECTIVE: Left ventricular hypertrophy (LVH) is an independent predictor of morbidity and mortality in dialysis patients. It remains unclear whether efforts to correct anemia in patients with mild-to-moderate chronic renal insufficiency (CRI) can reverse LVH. This prospective multi-center Chinese cohort study evaluates left ventricular mass index (LVMI) evolution in anemic CRI patients with or without recombinant human erythropoietin (rHuEPO) therapy. METHODS: Six centers enrolled 158 patients with serum creatinine from 147 to 400 micromol/L, and 86 of whom with hemoglobin (Hb) levels < 110 g/L received rHuEPO (Group A). Forty patients with comparable Hb levels (< 110 g/L) but did not receive rHuEPO (Group B) and those with Hb >/= 110 g/L (Group C, n = 32) were served as controls. Echocardiographic studies were performed to evaluate LVMI at baseline and every 3 months during a two-year period. RESULTS: At baseline, the prevalence of LVH was 72.1% in Group A, 72.5% in Group B and 59.4% in Group C. LVMI was inversely correlated with Hb levels (r = -0.70, P < 0.01). There was no difference in age, gender, aetiology of renal failure, blood pressure (BP) and cardiovascular risk factors between the 3 groups. The administration of rHuEPO in Group A significantly increased Hb levels from (93.8 +/- 14.6) g/L to (111.2 +/- 10.3) g/L and decreased LVMI from (142.6 +/- 25.7) g/m(2) to (132.4 +/- 18.5) g/m(2). The prevalence of LVH decreased 16.3% after a partial correction of anemia at 24 months, whereas Hb levels in controls (Group B and Group C) tended to decrease and LVMI significantly increased compared with baseline. The prevalence of LVH was significantly increased in Group B and C after 24 months. The percentage of patients whose serum creatinine level doubled during the follow-up was 3.4% in Group A, 15.0% in Group B and 9.4% in Group C, the difference between Group A and Group B being significant (P < 0.05). In addition, good BP control was obtained without any adverse effects. CONCLUSION: High prevalence of LVH was present in pre-dialysis CRI patients, which is associated with severity of anemia. Early treatment of anemia with rHuEPO can reverse LVH in CRI patients.