Peptidase inhibitor (PI16) impairs bladder cancer metastasis by inhibiting NF-κB activation via disrupting multiple-site ubiquitination of NEMO.

BACKGROUND: Bladder cancer (BLCA) is a malignancy that frequently metastasizes and leads to poor patient prognosis. It is essential to understand the molecular mechanisms underlying the progression and metastasis of BLCA and identify potential biomarkers. METHODS: The expression of peptidase inhibitor 16 (PI16) was analysed using quantitative PCR, immunoblotting and immunohistochemistry assays. The functional roles of PI16 were evaluated using wound healing, transwell, and human umbilical vein endothelial cell tube formation assays, as well as in vivo tumour models. The effects of PI16 on nuclear factor κB (NF-κB) signalling activation were examined using luciferase reporter gene systems, immunoblotting and immunofluorescence assays. Co-immunoprecipitation was used to investigate the interaction of PI16 with annexin-A1 (ANXA1) and NEMO. RESULTS: PI16 expression was downregulated in bladder cancer tissues, and lower PI16 levels correlated with disease progression and poor survival in patients with BLCA. Overexpressing PI16 inhibited BLCA cell growth, motility, invasion and angiogenesis in vitro and in vivo, while silencing PI16 had the opposite effects. Mechanistically, PI16 inhibited the activation of the NF-κB pathway by interacting with ANXA1, which inhibited K63 and M1 ubiquitination of NEMO. CONCLUSIONS: These results indicate that PI16 functions as a tumour suppressor in BLCA by inhibiting tumour growth and metastasis. Additionally, PI16 may serve as a potential biomarker for metastatic BLCA.

SBSN drives bladder cancer metastasis via EGFR/SRC/STAT3 signalling.

BACKGROUND: Patients with metastatic bladder cancer have very poor prognosis and predictive biomarkers are urgently needed for early clinical detection and intervention. In this study, we evaluate the effect and mechanism of Suprabasin (SBSN) on bladder cancer metastasis. METHODS: A tissue array was used to detect SBSN expression by immunohistochemistry. A tumour-bearing mouse model was used for metastasis evaluation in vivo. Transwell and wound-healing assays were used for in vitro evaluation of migration and invasion. Comprehensive molecular screening was achieved by western blotting, immunofluorescence, luciferase reporter assay, and ELISA. RESULTS: SBSN was found markedly overexpressed in bladder cancer, and indicated poor prognosis of patients. SBSN promoted invasion and metastasis of bladder cancer cells both in vivo and in vitro. The secreted SBSN exhibited identical biological function and regulation in bladder cancer metastasis, and the interaction of secreted SBSN and EGFR could play an essential role in activating the signalling in which SBSN enhanced the phosphorylation of EGFR and SRC kinase, followed with phosphorylation and nuclear location of STAT3. CONCLUSIONS: Our findings highlight that SBSN, and secreted SBSN, promote bladder cancer metastasis through activation of EGFR/SRC/STAT3 pathway and identify SBSN as a potential diagnostic and therapeutic target for bladder cancer.

Graphene Decorated with Uniform Ultrathin (CoP)x -(FeP)1-x Nanorods: A Robust Non-Noble-Metal Catalyst for Hydrogen Evolution.

Developing high-performance but low-cost hydrogen evolution reaction (HER) electrocatalysts with superior activity and stability for future sustainable energy conversion technologies is highly desired. Tuning of microstructure, configuration, and chemical composition are paramount to developing effective non-noble electrocatalysts for HER. Herein, a universal "nanocasting" method is reported to construct graphene decorated with uniform ternary (CoP)x -(FeP)1-x (0 ≤ x ≤ 1) nanorods hybrids with different chemical compositions [(CoP)x -(FeP)1-x -NRs/G] as a highly active and durable nonprecious-metal electrocatalyst for the HER. The optimized (CoP)0.54 -(FeP)0.46 -NRs/G electrocatalyst exhibits overpotentials of as low as 57 and 97 mV at 10 mA cm-2 , Tafel slopes of 52 and 62 mV dec-1 , exchange current densities of 0.489 and 0.454 mA cm-2 , and Faradaic efficiency of nearly 100% in acidic and alkaline media, respectively. More importantly, this electrocatalyst also exhibits high tolerance and durability in a wide pH range and keeps catalytic activity for at least 3000 cycles and 24 h of sustained hydrogen production. The excellent catalytic performance of the (CoP)x -(FeP)1-x -NRs/G electrocatalyst may be ascribed to its unique mesoporous structure and strong synergistic effect between CoP and FeP. Thus, the work provides a feasible way to fabricate cheap and highly efficient electrocatalyst as alternatives for Pt-based electrocatalysts for HER in electrochemical water splitting.

Relationship between methylenetetrahydrofolate reductase (MTHFR) A1298C gene polymorphism and type 2 diabetic nephropathy risk: a meta-analysis.

Relationship between methylenetetrahydrofolate reductase (MTHFR) A1298C gene polymorphism and type 2 diabetic nephropathy (T2DN) risk is still unclear. This study was performed to evaluate if there is an association between the MTHFR A1298C gene polymorphism and T2DN risk using meta-analysis. The relevant reports were searched and identified from PubMed, Cochrane Library on 1 October 2013, and eligible studies were included and synthesized. Eight reports were recruited into this meta-analysis for the association of the MTHFR A1298C gene polymorphism with T2DN risk. The MTHFR A1298C C allele or CC genotype was shown to be not associated with T2DN risk (C allele: OR = 0.76, 95% CI: 0.43-1.34, p = 0.34; CC genotype: OR = 1.18, 95% CI: 0.63-2.22, p = 0.60). Interestingly, AA genotype was associated with the T2DN risk (OR = 0.68, 95% CI: 0.49-0.96, p = 0.03). In the sensitivity analysis according to the Hardy-Weinberg equilibrium (HWE), the results were consistent with those in non-sensitivity analysis. However, in the sensitivity analysis according to the control source from hospital, sample size of case (≥ 100), sample size of case (<100), the MTHFR A1298C gene polymorphism was not associated with T2DN risk. In conclusion, the MTHFR A1298C gene polymorphism was not associated with T2DN risk. However, additional studies are required to firmly establish a correlation between the MTHFR A1298C gene polymorphism and T2DN risk.

1,5-Bis[1-(4-bromo-phen-yl)ethyl-idene]thio-carbonohydrazide.

The asymmetric unit of the title compound, C17H16Br2N4S, contains two independent mol-ecules in which the benzene rings form dihedral angles of 20.0 (1) and 55.3 (1)°. In the crystal, a pair of N-H⋯S hydrogen bonds link the two different independent mol-ecules into a dimer.

Aqua-trimeth-yl[2-(4-methyl-pyrimidin-2-ylsulfan-yl)acetato-κO]tin(IV).

In the title compound, [Sn(CH3)3(C7H7N2O2S)(H2O)], the Sn(IV) atom has a distorted trigonal-bipyramidal coordination geometry, with one carboxyl-ate O atom of the 2-(4-methyl-pyrimidine-2-sulfan-yl)acetate ligand and the O atom of a water mol-ecule in axial positions, and three methyl groups in equatorial positions. In the crystal, mol-ecules are linked via O-H⋯O and O-H⋯N hydrogen bonds, forming double-stranded chains propagating along [010].

Identification of serum miR-378 and miR-575 as diagnostic indicators and predicting surgical prognosis in human epilepsy.

Background: Epilepsy (EP) is a common neurological disorder which is characterized by excessive abnormal synchronization of neuronal discharges in the brain due to chronic recurrent seizures of multiple etiologies. Variety of microRNAs have been associated with the occurrence and development of EP. This study aimed to determine the aberrant expression of miR-378 and miR-575 in EP patients to validate their potential to distinguish EP from healthy patients. Methods: RT-qPCR was used to determine the expressions of miR-378 and miR-575 from serum specimens of 106 EP and 103 control individuals. Clinical indicators between EP patients and controls were assessed. Based on surgical outcome, EP patients were further divided into Engel I-IV EP. The potentials of miR-378 and miR-575 in discriminating EP from healthy participants and predicting surgical prognosis were calculated by receiver operating characteristic (ROC) analysis. Results: We found the miR-378 and miR-575 were significantly declined (P<0.001) in Engel I-II and III-IV EP patients with no difference in clinical parameters compared. Moreover, miR-378 and miR-575 displayed high sensitivity, specificity, and accuracy in distinguishing EP patients and predicting surgical outcomes. Moreover, after surgical treatment, miR-378 and miR-575 levels were increased compared with those at admission, suggesting their potentials in treatment response. Conclusions: miR-378 and miR-575 could be utilized as novel and non-invasive serum biomarkers in discriminating EP from healthy controls and predicting surgical outcome, shedding new insights on epileptogenesis and EP treatment.

Insight into the spatial interaction of D-π-A bridge derived cyanines and nitroreductase for fluorescent cancer hypoxia detection.

Nitroreductase (NTR) detection in tumor is critical because NTR level is correlated with hypoxia degree and cancer prognosis. With the feature of high sensitivity and selectivity, fluorescence organic probes for NTR detection exhibited a promising future for tumor hypoxia detection. However, the discovery and design of such probes have been impeded due to the lack of the understanding of spatial match and mismatch of these probes with NTR. Here, we have developed two new nitrophenyl-functionalized trimethincyanine (Cy3) probes with para- or meta- positions of nitro-group in phenyl ring. Para-nitrophenyl substituted Cy3 (pNP-Cy3) exhibited a remarkable response to NTR (20-fold fluorescence enhancement) with good selectivity and sensitivity. Experimental and theoretical analysis verified that the substituent position of nitro group on phenyl ring of dyes altered the spatial arrangement of nitro-substituent group, thereby modulated the spatial match and mismatch between Cy3 dyes and binding domain of NTR, and consequently led to a different fluorescent turn-on response. In tumor-bearing mice model, hypoxia status of A549 xenografted tumor of mice was successfully delineated by using pNP-Cy3. These results may provide a clue for designing new cyanine-derived NTR probe to monitor NTR-overexpressed hypoxia cancer cells.

Aconitine: A review of its pharmacokinetics, pharmacology, toxicology and detoxification.

ETHNOPHARMACOLOGICAL RELEVANCE: Aconitine, a C19-norditerpenoid alkaloid, derives from many medicinal plants such as Aconitum carmichaelii Debx. (Chinese:), Aconitum kusnezoffii Reichb (Chinese:), which were used to rheumatic fever, painful joints and some endocrinal disorders. AIMS OF THE REVIEW: The present paper reviews research progress relating to the pharmacokinetics, physiological and pathological processes of aconitine, while some promising research direction and the detoxification of aconitine are also discussed. MATERIALS AND METHODS: The accessible literature on aconitine, from 1990 to 2020, obtained from published materials of electronic databases, such as SCI finder, PubMed, Web of Science, Science Direct, Springer and Google Scholar was systematically analyzed. RESULTS: In this review, we address the pharmacokinetics of aconitine, as well as its pharmacological effects including anti-cancer, anti-inflammatory, anti-virus, immunoregulation, analgesic, insecticide and inhibition of androgen synthesis. Further, we summarize the toxicity of aconitine such as cardiotoxicity and neurotoxicity, on which we strikingly focus on the ways to reduce the toxicity of aconitine based. CONCLUSIONS: Aconitine plays an vital role in a wide range of physiological and pathological processes and we can reduce the toxicity of aconitine by compatibility and hydrolysis. Although some issues still exist, such as the correlative relationship between the dose and toxicity of aconitine not being clear, our review may provide new ideas for the application of aconitine in the treatment of related diseases.

Psychometric Properties of the Chinese Translated Athlete Burnout Questionnaire: Evidence From Chinese Collegiate Athletes and Elite Athletes.

The purpose of the study was to translate the athlete burnout questionnaire (ABQ) into Simplified Chinese and examine its psychometric properties in Chinese collegiate athletes and elite athletes. Firstly, the factor structure, internal consistency reliability and nomological validity of the Chinese translated ABQ was examined in a sample of Chinese collegiate athletes (n = 214, 58.9% females). Secondly, abovementioned psychometric properties were examined in a sample of Chinese elite athletes (n = 505, 52.7% females). Finally, measurement invariance of the Chinese translated ABQ was examined across the two samples. It was found that the 12-item three-correlated-factors model outperformed the one factor model and bi-factor model in collegiate athlete sample whereas the 12-item bi-factor model best represented the factor structure of the Chinese translated ABQ in elite athlete sample. Satisfactory internal consistency reliabilities of the Chinese translated ABQ were evidenced in the two samples. Nomological validity was also supported by the results of the two samples that the three subscales of the ABQ were significantly associated with its theoretically related variables. Results of multiple-group confirmatory factor analysis revealed that weak measurement invariance of the Chinese translated ABQ (three-correlated-factors model) was evidenced across the two samples. Collectively, results of this study indicated that the 12-item Chinese translated ABQ could be used for measuring burnout of Chinese collegiate and elite athletes. Significance and implication of the current study as well as recommendations for future study were discussed.

Extracellular vesicles-transferred SBSN drives glioma aggressiveness by activating NF-κB via ANXA1-dependent ubiquitination of NEMO.

Glioma is the most common malignant primary brain tumor with aggressiveness and poor prognosis. Although extracellular vesicles (EVs)-based cell-to-cell communication mediates glioma progression, the key molecular mediators of this process are still not fully understood. Herein, we elucidated an EVs-mediated transfer of suprabasin (SBSN), leading to the aggressiveness and progression of glioma. High levels of SBSN were positively correlated with clinical grade, predicting poor clinical prognosis of patients. Upregulation of SBSN promoted, while silencing of SBSN suppressed tumorigenesis and aggressiveness of glioma cells in vivo. EVs-mediated transfer of SBSN resulted in an increase in SBSN levels, which promoted the aggressiveness of glioma cells by enhancing migration, invasion, and angiogenesis of recipient glioma cells. Mechanistically, SBSN activated NF-κB signaling by interacting with annexin A1, which further induced Lys63-linked and Met1-linear polyubiquitination of NF-κB essential modulator (NEMO). In conclusion, the communication of SBSN-containing EVs within glioma cells drives the formation and development of tumors by activating NF-κB pathway, which may provide potential therapeutic target for clinical intervention in glioma.

2-Amino-4-[4-(dimethyl-amino)-phen-yl]-5-oxo-5,6,7,8-tetra-hydro-4H-chromene-3-carbonitrile.

In the title mol-ecule, C(18)H(19)N(3)O(2), the fused cyclo-hexenone and pyran rings adopt sofa conformations. Inter-molecular N-H⋯N and N-H⋯O hydrogen bonds link mol-ecules into corrugated layers parallel to the bc plane.

2-Amino-4-(2-chloro-phen-yl)-5-oxo-5,6,7,8-tetra-hydro-4H-chromene-3-carbonitrile ethanol monosolvate.

In the title compound, C(16)H(13)ClN(2)O(2)·C(2)H(6)O, the fused cyclo-hexene and pyran rings adopt envelope and flattened boat conformations, respectively. In the crystal, N-H⋯O and O-H⋯O hydrogen bonds link the chromene and ethanol solvent mol-ecules into infinite chains along the c axis, and N-H⋯N hydrogen bonds link these chains into a three-dimensional framework. Weak C-H⋯π inter-actions are also present.

2-Amino-4-(4-meth-oxy-phen-yl)-5-oxo-5,6,7,8-tetra-hydro-4H-chromene-3-carbonitrile.

The title compound, C(17)H(16)N(2)O(3), crystallizes with two independent mol-ecules in the asymmetric unit. In both mol-ecules, the fused cyclo-hexenone ring adopts a sofa conformation. In the crystal, N-H⋯N and N-H⋯O hydrogen bonds link the mol-ecules into corrugated layers parallel to the (101) plane.

Albumin-based fluorescence resonance energy transfer nanoprobes for multileveled tumor tissue imaging and dye release imaging.

Tumor tissue imaging and drug release imaging are both crucial for tumor imaging and image-guided drug delivery. It is urgent to develop a multileveled tumor imaging platform to realize the multiple imaging applications. In this work, we synthesized an albumin-based fluorescence resonance energy transfer (FRET) probe Cy5/7@HSA NPs containing two near-infrared cyanine dyes (CyBI5 and CyBI7) with high FRET efficiency (97 %). Excellent brightness and efficient FRET inside Cy5/7@HSA NPs enabled high-sensitive cell imaging and tumor imaging. This unique nanoprobe imaged 4T1 tumor-bearing mice with high sensitivity (TBR = 5.2) at 24 h post-injection and the dyes penetrated the tumor interior around 4 h post-injection. The release of dyes from nanoprobes was also tracked. This result shows the strong potential of this albumin-based FRET nanoprobe as multileveled tumor imaging platform for in vivo tumor imaging, drug delivery and image-guided surgery.

Laparoscopy-assisted total gastrectomy with extended lymph node resection for advanced gastric cancer--reports of 82 cases.

BACKGROUND/AIMS: As a result of increased surgeon's experience and the improvement in laparoscopic techniques, laparoscopic gastrectomy has been widely accepted for the management of early stage gastric cancer. Sufficient evidence has demonstrated the feasibility of laparoscopy-assisted distal gastrectomy for early gastric cancer. Radical laparoscopic treatment of more advanced gastric cancer is controversial. The purpose of the current study was to determine feasibility and advantage of laparoscopy-assisted total gastrectomy (LTG) versus open total gastrectomy (OTG) with D2 dissection of lymph nodes in patients with advanced gastric cancer. METHODOLOGY: Between Nov 2005 and May 2009 in our single institute, 176 patients with advanced gastric cancer underwent total gastrectomy with D2 dissection of lymph nodes. 82 of these patients underwent LTG, 94 underwent OTG. Clinical data of the both procedures were compared. Disease-free survival was studied to assess short-term outcome differences between the groups. RESULTS: None of 82 patients was converted to laparotomy and no operative mortality was observed in LTG. Postoperative complication rate was 9.8% (8/82) in LTG, compared with 24.5% (23/94) in OTG. No major complications occurred among the all patients who underwent LTG. There were 2 deaths (2/94) due to myocardial infarction in 3 days after OTG. In comparison to OTG, LTG had the longer operating time (275 +/- 78 versus 212 +/- 51 min; p < 0.001), similar number of lymph nodes (34.2 +/- 13.5 versus 36.4 +/- 19.1; p = 0.331), less operative blood loss (156 +/- 112 ml versus 339 +/- 162 ml; p < 0.001), earlier recovery of bowel activity, earlier ambulation and reduced postoperative pain after surgery (p < 0.001). Tumor- free margins were obtained in all patients who underwent LTG. In a mean follow-up period of 22.5 months, local recurrence and metastasis were observed in 19 of 82 patients in LTG, 23 of 94 patients in OTG respectively. CONCLUSIONS: Laparoscopically assisted total gastrectomy for middle and upper gastric cancer is considered to be a safe and feasible procedure. Short-term oncological outcomes for laparoscopic total gastrectomy with extended lymph nodes were the same as in open surgery.

1-(1-Phenyl-ethyl-idene)carbonohydrazide.

The title compound, C(9)H(12)N(4)O, crystallizes with two independent mol-ecules in the asymmetric unit. In the crystal, inter-molecular N-H⋯O and N-H⋯N hydrogen bonds link the mol-ecules into paired ribbons propagated in [100]. The crystal studied was a twin (twin law 00/00/001) with a minor component of 25%.

(3-Hydroxy-2-{[1-(2-oxidophenyl)ethyl-idene]amino-κO,N}propanoato-κO)diphenyltin(IV).

In the title compound, [Sn(C(6)H(5))(2)(C(11)H(11)NO(4))], the tin(IV) atom is penta-coordinated in a distorted trigonal-bipyramidal SnC(2)NO(2) geometry. In the crystal structure, inter-molecular O-H⋯O hydrogen bonds link the mol-ecules into centrosymmetric dimers. Weak C-H⋯O inter-actions further link the dimers into chains extending in [010].

1,5-Bis(1-phenyl-ethyl-idene)carbonohydrazide.

In the title mol-ecule, C(17)H(18)N(4)O, the two phenyl rings form a dihedral angle of 18.15 (17)°. In the crystal, pairs of inter-molecular N-H⋯O hydrogen bonds link the mol-ecules into centrosymmetric dimers. Weak inter-molecular C-H⋯O inter-actions further link the dimers into chains running along [010].

[Influence of warming needling technique on gastrointestinal reaction after hyperthermic intrape-ritoneal chemotherapy in patients with postoperation of colon cancer].

OBJECTIVE: To observe the effect of warming needling therapy on gastrointestinal reaction after hyperthermic intraperitoneal chemotherapy (HIPEC) in patients of spleen and stomach deficiency syndrome after colon cancer surgery. METHODS: A total of 120 cases of HIPEC were randomized into observation group and control group, 60 cases in each. The patients of the two groups all received HIPEC. In the observation group, 1 h before HIPEC, warming needling technique was applied to Zusanli (ST36), Sanyinjiao (SP6) and Yinlingquan (SP9) and the even-needing technique of acupuncture was applied to Neiguan (PC6) for 30 min, and then the intravenous injection with Ondansetron was given 30 min before HIPEC. In the control group, The intravenous injection with Ondansetron was given 30 min before HIPEC. In the two groups, the changes in nausea, vomiting, abdominal distention, diarrhea, total bilirubin (TB), alanine aminotransferase (ALT), alkaline phosphatase (ALP) and KPS score, as well as the average hospitalization length of stay were observed. RESULTS: The total effective rates in the treatment of nausea, vomiting, abdominal distention and diarrhea were 91.67%(55/60), 93.33%(56/60), 80.00%(48/60) and 88.33%(53/60) in the observation group and were 78.33%(47/60), 78.33%(47/60), 63.33%(38/60) and 70.00%(42/60) in the control group respectively, and the total effective rate in the treatment of gastrointestinal reaction of HIPEC in the observation group was obviously higher than that in the control group(P<0.05). The KPS score and curative effect in the observation group was obviously higher than those of the control group(P<0.05), and the average hospitalization length of stay in the observation group was obviously reduced as compared with the control group (P<0.05). There were no significant differences in serum TB, ALT and ALP contents between the two groups after treatment (P>0.05). CONCLUSION: The warming needling technique of acupuncture and moxibustion alleviates the gastrointestinal reaction, improves KPS score and reduces the hospitalization length of stay in HIPEC patients after the surgery of colon cancer and differentiated as the spleen and stomach deficiency in traditional Chinese medicine.