Nitric oxide alleviates programmed cell death induced by cadmium in Solanum lycopersicum seedlings through protein S-nitrosylation.

Cadmium (Cd), as a non-essential and toxic heavy metal in plants, has deleterious effects on plant physiological and biochemical processes. Nitric oxide (NO) is one of the most important signaling molecules for plants to response diverse stresses. Here, we found that Cd-induced programmed cell death (PCD) was accompanied by NO bursts, which exacerbated cell death when NO was removed and vice versa. Proteomic analysis of S-nitrosylated proteins showed that the differential proteins in Cd-induced PCD and in NO-alleviated PCD mainly exist together in carbohydrate metabolism and amino acid metabolism, while some of the differential proteins exist alone in metabolism of cofactors and vitamins and lipid metabolism. Meanwhile, S-nitrosylation of proteins in porphyrin and chlorophyll metabolism and starch and sucrose metabolism could explain the leaf chlorosis induced by PCD. Moreover, protein transport protein SEC23, ubiquitinyl hydrolase 1 and pathogenesis-related protein 1 were identified to be S-nitrosylated in vivo, and their expressions were increased in Cd-induced PCD while decreased in NO treatment. Similar results were obtained in tomato seedlings with higher S-nitrosylation. Taken together, our results indicate that NO might be involved in the regulation of Cd-induced PCD through protein S-nitrosylation, especially proteins involved in PCD response.

Hydrogen gas: A new fresh keeping agent of perishable horticultural products.

Hydrogen gas (H2), a gaseous signaling molecule, is involved in plant growth and development. This review collates emerging evidence to show that H2 regulates the postharvest senescence of horticultural products through critical biochemical processes, including the improvement of antioxidant systems, the activation of cell wall metabolism, the promotion of energy metabolism, the inhibition of ethylene biosynthesis and the regulation of bacterial communities. Additionally, the interactions between H2 and other signaling molecules are also discussed. This paper presents the current status of H2 research in terms of its biological effects and safety in postharvest products by combining the research results on the molecular mechanisms of biological effects and H2 signaling. The action mechanism of H2 for postharvest preservation is also proposed, and it reflects the complexity and diversity of the pathways involved. Furthermore, a growing body of evidence has found a large number of downstream pathways or targets for the medical effects of H2. Therefore, the scientific and practical aspects of H2 biology are proposed for the postharvest preservation of horticultural products.

Algal blooms modulate organic matter remineralization in freshwater sediments: A new insight on priming effect.

This study provides a novel insight into the degradation of sediment organic matter (SOM) regulated by algae-derived organic matter (AOM) based on priming effect. We tracked the dynamics of SOM mineralization products and pathways, together with priming effects (PE) using the compound-specific stable isotope (δ13C) technique following addition of low- and high-density algal debris in sediments. We found that algal debris increased the total carbon oxidation rate, and resulted in denitrification and methanogenesis-dominated SOM mineralization. While iron reduction and sulphate reduction played important roles in the early period of algal accumulation. Total carbon oxidation rate and anaerobic rates (Ranaerobic) were higher in the amended treatments compared with that in the control. Analysis indicated that algal debris had a positive PE on SOM mineralization, which caused an intensified mineralization in the initial phase with over 80% of dissolved inorganic carbon deriving from SOM degradation. Total carbon oxidation rate of SOM deduced from priming effect (RTCOR-PE) was similar to Ranaerobic, further indicating SOM mineralization was a critical source of the end products. These findings deviate the causal focus from the decomposition of AOM, and confirm the accumulation of AOM as the facilitator of SOM mineralization. Our study offers empirical evidences to advance the traditional view on the effect of AOM on SOM mineralization.

Identification of potential impacts of climate change and anthropogenic activities on streamflow alterations in the Tarim River Basin, China.

Understanding contributions of climate change and human activities to changes in streamflow is important for sustainable management of water resources in an arid area. This study presents quantitative analysis of climatic and anthropogenic factors to streamflow alteration in the Tarim River Basin (TRB) using the double mass curve method (DMC) and the Budyko methods. The time series (1960~2015) are divided into three periods: the prior impacted period (1960~1972) and the two post impacted periods, 1973~1986 and 1987~2015 with trend analysis. Our results suggest that human activities played a dominant role in deduction in the streamflow in TRB with contribution of 144.6% to 120.68% during the post impacted period I and 228.68% to 140.38% during the post impacted period II. Climatic variables accounted for 20.68%~44.6% of the decrease during the post impacted period I and 40.38% ~128.68% during the post impacted period II. Sensitivity analysis indicates that the streamflow alteration was most sensitive to changes in landscape parameters. The aridity index and all the elasticities showed an obvious increasing trend from the upstream to the downstream in the TRB. Our study suggests that it is important to take effective measures for sustainable development of eco-hydrological and socio-economic systems in the TRB.

Expression and prognostic significance of MAP4K4 in lung adenocarcinoma.

Accumulating evidence indicates that mitogen-activated protein 4 kinase 4 (MAP4K4) is frequently overexpressed in many types of human cancers, and plays important roles in transformation, invasiveness, adhesion, and cell migration. The aim of the present study was to explore the expression and prognostic significance of MAP4K4 in lung adenocarcinoma. The results of real-time quantitative PCR and Western blotting analysis revealed an enhanced expression of MAP4K4 in lung adenocarcinomas relative to adjacent non-tumorous lung tissues at both transcriptional and translational levels. Immunohistochemistry showed that 130 of 309 (42%) lung adenocarcinomas had high expression of MAP4K4. MAP4K4 overexpression was significantly correlated with histological grade (p=0.027), pT status (p=0.048), pN status (p=0.006), and pleural invasion (p=0.024). Patients with high MAP4K4 expression had a shorter overall survival compared with those with low MAP4K4 expression, regardless of histological grade, pT status, pN status, or pleural invasion status. Multivariate analysis identified MAP4K4 as an independent prognostic factor for lung adenocarcinoma. In conclusion, our results demonstrate that elevated MAP4K4 expression is closely associated with lung adenocarcinoma progression and has an independent prognostic value in predicting overall survival for patients with lung adenocarcinoma.

Expression and prognostic significance of centromere protein A in human lung adenocarcinoma.

BACKGROUND: Centromere protein A (CENP-A), one of the fundamental components of the human active kinetochore, is frequently upregulated in many cancers and plays important roles in cell cycle regulation, cell survival, and genetic stability. The aim of the present study was to explore the expression and prognostic significance of CENP-A in lung adenocarcinoma. EXPERIMENTAL DESIGN: The expression of CENP-A was detected in 20 fresh human lung adenocarcinoma specimens and corresponding non-tumorous lung tissues by real-time polymerase chain reaction (RT-PCR) and Western blotting analysis. Using immunohistochemistry, we analyzed CENP-A protein expression in additional 309 lung adenocarcinomas. The clinicopathological and prognostic significance of CENP-A expression was analyzed. RESULTS: RT-PCR and Western blotting analysis revealed an enhanced expression of CENP-A in lung adenocarcinomas relative to adjacent non-tumorous lung tissues at both transcriptional and translational levels. Immunohistochemistry showed that 146 of 309 lung adenocarcinomas (47.3%) had high expression of CENP-A. CENP-A overexpression was significantly correlated with pathological grade (P=0.009), pT status (P=0.017), pN status (P=0.002), pleural invasion (P=0.013), high Ki-67 expression (P=0.003), and P53 positivity (P=0.001). Patients with high CENP-A expression had shorter overall survival time compared with those with low CENP-A expression. Multivariate analysis identified CENP-A as an independent prognostic factor for lung adenocarcinoma. CONCLUSION: Our results demonstrate that elevated CENP-A expression is closely associated with lung adenocarcinoma progression and has an independent prognostic value in predicting overall survival for patients with lung adenocarcinoma.

Intrahepatic cholangiocarcinoma arising in multiple bile duct hamartomas: report of two cases and review of the literature.

Multiple bile duct hamartomas (BDHs)/von Meyenburg complexes, are tumor-like lesions of the liver. Malignant transformation in BDHs has been previously reported in very rare instances, and the most common tumor arising in this clinical setting is cholangiocarcinoma. Herein, we report on clinicopathological findings in two cases of cholangiocarcinoma occurring in liver with multiple BDHs. Histopathologically, multiple BDHs showed morphologic transition from clearly benign to dysplasia or carcinoma in situ, then to invasive carcinoma sequence of the biliary epithelium. The neoplastic epithelium showed positivity for cytokeratin 19, CA 19-9, and epithelial membrane antigen. Staining for Hep Par 1, alpha-fetoprotein, cytokeratin 20, and alpha1-antitrypsin was negative. All sections from the non-neoplastic liver in each specimen showed multiple BDHs. Any other clinically detectable primary tumor was not found. These two neoplasms were interpreted as a cholangiocarcinoma arising in BDHs. This suggested BDHs might be a risk factor of development of cholangiocarcinoma.

Clinicopathologic significance of mitotic arrest defective protein 2 overexpression in hepatocellular carcinoma.

Mitotic arrest defective protein 2 (MAD2) gene plays a central role in the mitotic checkpoint. Elevated MAD2 expression was observed in a number of human malignancies; its role in the development of hepatocellular carcinoma is still not understood and is controversial. The purpose of this study was to investigate the clinicopathologic significance of MAD2 expression in hepatocellular carcinoma. The MAD2 protein and its messenger RNA levels were measured in hepatocellular carcinomas, high-grade dysplastic nodules, and their paired nontumorous liver tissues by quantitative real-time polymerase chain reaction, Western blot, and immunohistochemistry. The results showed that MAD2 at both messenger RNA and protein levels was overexpressed in 8 of 9 high-grade dysplastic nodules and in 51 of 58 hepatocellular carcinomas, including 12 of 14 unifocal small hepatocellular carcinomas. There was a tendency for MAD2 expression to increase in the process of this multistep carcinogenesis. A significantly high tumor MAD2 immunostaining was associated with the progression of histologic grade and the overall low survival. In conclusion, MAD2 is overexpressed frequently in hepatocellular carcinoma, including high-grade dysplastic nodules and early-stage small hepatocellular carcinoma, indicating that overexpression of MAD2 plays a role in the development and progression of hepatocellular carcinoma. It may be an early event in hepatocarcinogenesis and could be used as a potential prognostic indicator.

Malignant angiomyolipoma in the liver: a case report with pathological and molecular analysis.

Malignant angiomyolipoma (AML) of the liver is rare. We report a case of AML with malignant transformation and metastases. A 30-year-old man had developed giant hepatic masses. Microscopically, the periphery of the tumor showed components of classic hepatic AML, but the central region contained atypical epithelioid components with extremely pleomorphic and hyperchromatic nuclei with frequent mitotic figures. Immunohistochemical analysis revealed that the epithelioid cells were positive for HMB-45 and smooth muscle actin. Furthermore, the atypical epithelioid cells displayed P53 immunoreactivity and mutation at exon 7 for p53. The tumor showed a typical monoclonal pattern but no loss of heterozygosity or microsatellite instability. Markedly atypical epithelioid cells with vascular invasion, distant metastasis, and fatal outcome were interpreted as malignant characteristics of hepatic AML. It is suggested that large tumor size, pleomorphic nuclei with high proliferation activity, and P53 immunoreactivity may predict the existence of malignant transformation of hepatic AML.

Downregulated expression of metallothionein and its clinicopathological significance in hepatocellular carcinoma.

AIM: Metallothionein (MT) protein is related to different stages of development and progression of various tumors in humans. The aim of the present study was to investigate expression and localization of MT and their association with clinicopathological characteristics in hepatocellular carcinoma (HCC). METHODS: Histological specimens of 400 HCC with corresponding non-cancerous liver tissues were stained for MT (E9), P53 and Ki-67 by immunohistochemical staining using tissue microarrays. RNA expression of MT-1X and MT-2A isoforms was determined by real-time reverse transcription-polymerase chain reaction in a set of independent samples of 161 HCC. RESULTS: Downregulated expression of MT at both mRNA and protein levels was detected in HCC, compared with non-cancerous liver tissues. The frequencies of MT positivity were significantly lower in cases with positive hepatitis B surface antigen than in those with negative hepatitis B surfaceantigen (P = 0.042). The positive rate of MT expression was more frequent in tumors 2 cm in diameter (P = 0.007). There was a tendency for MT expression to decrease with the progression of histological grade. Mainly nuclear expression of MT correlated with poorly differentiated HCC. No statistical correlation was found between P53, Ki-67 and MT expression. CONCLUSIONS: Downregulated expression of MT in HCC may play a role in hepatocarcinogenesis and be a marker of hepatocellular differentiation. Hepatitis B virus infection may be correlated to downregulated expression of MT. The mainly nuclear MT immunostaining may reflect an aggressive behavior in poorly differentiated HCC.