TGF-? is an important biological mediator. It regulates a wide range of functions including embryonic development, wound healing, organ development, immuno-modulation, and cancer progression. Interestingly, TGF-? is known to inhibit cell growth in benign cells but promote progression in cancer cells, a phenomenon known as TGF-? paradox. TGF-? stimulation in cancer cells leads to a differential Erk activation, which srves as the basis of TGF-? paradox between benign and cancer cells. The critical events of TGF-? mediated Erk activation are suppressed TBRs and elevated TGF-? in tumor cells but not in benign cells. These events form the basis of the "vicious cycle of TGF-? signaling". The term "vicious cycle", implies that, with each advancing cycle of TGF-? signaling, the tumor will accumulate more TGF-? and will be more "aggressive" than that of the previous cycle. Understanding this vicious cycle of TGF-? signaling in tumor progression and metastasis will help us to predict indolent from aggressive cancers and will help us to develop novel anti-cancer strategies.
TGF-? regulates a wide range of biological functions including embryonic development, wound healing, organogenesis, immune modulation, and cancer progression. Interestingly, TGF-? is known to inhibit cell growth in benign cells but promote progression in cancer cells; this phenomenon is known as TGF-? paradox. To date, the mechanism of this paradox still remains a scientific mystery. In this review, we present our experience, along with the literature, in an attempt to answer this mystery. First, we observed that, on TGF-? engagement, there is a differential activation of Erk between benign and cancer cells. Since activated Erk is a major mediator in tumor progression and metastasis, a differentially activated Erk represents the answer to this mystery. Second, we identified a key player, PP2A-B56?, which is differentially recruited by the activated type I TGF-? receptor (TBRI) in benign and tumor cells, resulting in differential Erk activation. Finally, TGF-? stimulation leads to suppressed TBRs in tumor cells but not in benign cells. This differentially suppressed TBRs triggers differential recruitment of PP2A-B56? and, thus, differential activation of Erk. The above three events explain the mysteries of TGF-? paradox. Understanding the mechanism of TGF-? paradox will help us to predict indolent from aggressive cancers and develop novel anti-cancer strategies.
This systematic review summarizes evidence on allotransplantation of donor kidneys after resection of a small renal cancer or contralateral healthy kidneys from cadaveric donors with unilateral renal cancer. Eligible studies were identified by screening four bibliographic databases, contacting key authors, and analyzing the bibliographies of included studies. Two reviewers independently assessed the reports for inclusion and extracted data, which were summarized as a narrative review. In the 20 case report or case series studies included in the analysis, there were 97 documented cases of donor kidney transplantation after resection of small renal cancer without pathologically confirmed recurrence, whereas 22 cases used contralateral healthy kidneys from cadaveric donors with unilateral renal cancer with one case of cancer recurrence. These results suggest that the use of donor kidneys after resection of small renal cancer is associated with a relatively low cancer recurrence rate.
This study used 16S rRNA gene-based pyrosequencing (16S-pyrotag) to investigate both planktonic and benthic bacterial communities in two main tributaries (North River and West River) of the Jiulong River Watershed (JRW), a mesoscale subtropical watershed that has experienced intensive human perturbation in recent decades. The results of 16S-pyrotag showed that benthic bacterial communities were clearly more diverse and uniform than surface bacterioplankton communities. The results of taxonomic assignments indicated that Betaproteobacteria, Actinobacteria and Firmicutes were significantly more abundant in planktonic than in benthic communities, whereas the relative abundances of Acidobacteria, Delta-, Gammaproteobacteria, Chloroflexi and Nitrospira were higher in sediment than in water samples. In particular, several sewer- and fecal-pollution bacterial indicators were observed in water samples, implying that the water bodies of the JRW were contaminated by fecal pollution. Using the typical freshwater bacteria (TFB) taxonomic framework, 57.6±10%, 27.6±10.9% and 10.4±6.9% of sequences recovered from planktonic communities could be assigned to lineages, clades and tribes of TFB, respectively. The relatively lower abundance of TFB implied that some unknown or unique autochthonous bacterioplankton populations occurred in the JRW. The principal coordinate analysis (PCoA) and one way analysis of similarity (ANOSIM) analysis demonstrated that planktonic bacterial community structures were significantly different between North River and West River, whereas benthic communities from these two tributaries were grouped together. Multivariate statistical analysis revealed that nutrient concentrations and stoichiometry were the key drivers of both ?- and ?-diversity patterns of bacterioplankton communities. Overall, our results indicate that the diversity, composition and structure of planktonic bacterial communities are sensitive to water chemistry (e.g., nutrient concentrations and stoichiometry) in the JRW, and therefore can serve as a good sentinel of environmental changes in this watershed.
Box-Behnken design including independent variables such as extraction temperature (60-80°C), extraction time (20-40 min) and ratio of water to raw material (30-50 mL/g) was used to optimize the extraction process of Bruguiera gymnorrhiza polysaccharides (BGPs). The experimental data were fitted to a second-order polynomial equation using multiple regression analysis. The optimum conditions were predicted as follows: extraction temperature 71°C, extracting time 31.4 min, and ratio of water to raw material 42. Under these conditions, the yield of BGPs obtained was (16.43 ± 0.08)%, which was in good agreement with the predicted value 16.47%. Additionally, characterization of BGPs was obtained by FT-IR analysis. The antioxidant activities of BGPs were evaluated in vitro. BGPs demonstrated appreciable antioxidant potential on superoxide anion radical, ABTS radical, and hydroxyl radical scavenging. These may provide theoretical basis for further system research and rational development and utilization of mangrove resources.
The worry of potential residual renal cancer cells in donor kidney after resection of small renal cancer impedes the extensive use of such controversial donor source. To explore the impacts of organ preservation process on the survival of renal cancer cells, we detected cell proliferation and viability of benign and malignant renal cell lines and clinical renal samples after treated with simulated organ preservation process. It was found that the viability and proliferation of malignant renal cells are inhibited much more than that of benign renal cells during prolonged organ preservation. The inhibition of proliferation in benign renal cells is fully reversible, while in malignant renal cancer cells is not fully reversible after a certain time. So potential residual renal cancer cells could be partly inhibited and eliminated by organ preservation process.
DNA methyltransferase (DNMT) is one of the major factors mediating the methylation of cancer related genes such as TGF-? receptors (T?Rs). This in turn may result in a loss of sensitivity to physiologic levels of TGF-? in aggressive prostate cancer (CaP). The specific mechanisms of DNMTs role in CaP remain undetermined. In this study, we describe the mechanism of TGF-?-mediated DNMT in CaP and its association with clinical outcomes following radical prostatectomy.
To study the correlation between the levels of IFN-? and IL-4 and the expression of Fas and Bcl-2 in peripheral blood lymphocytes (PBL) in hemodialysis patients, the indirect immune fluorescein labeling method of flow cytometry and solid sandwich enzyme-linked immunosorbent assay were performed for detecting the expression of Fas and Bcl-2 in PBL and the levels of IFN-? and IL-4 in the serum of 30 hemodialysis patients, respectively. It was found that the expression of Fas in PBL and the level of IL-4 in the serum of hemodialysis patients were significantly higher (P < 0.01), whereas Bcl-2 in PBL and IFN-? in the serum were significantly lower (P < 0.01) than those of the normal controls. According to statistical analysis, the expression of Fas in PBL had a negative correlation with the level of IFN-?, but a positive correlation with IL-4 in the serum of hemodialysis patients. Contrarily, the expression of Bcl-2 had a positive correlation with IFN-?, but a negative correlation with IL-4 in the serum of hemodialysis patients. These results suggest that hemodialysis patients have a suppressed secretion of Th1-associated cytokine IFN-?, but an increased secretion of Th2-associated cytokines IL-4, and these two aspects may play an important role in the abnormal apoptosis of PBL and its accompanying immune deficiency.
Measurements were conducted during 2004-2005 and 2009-2010 to characterize atmospheric nitrogen (N) deposition to the Jiulong River Estuary - Xiamen Bay area in southeast China. Isotopic analysis and long-term data (1990-2009) for inorganic N extracted from the national acid deposition dataset were used to determine the dominant source of atmospheric nitrate and N component dynamics. The results showed that the mean dissolved total N concentration in rain water for the three coastal area sites was 2.71 ± 1.58 mg N L(-1) (n = 141) in 2004. The mean dissolved inorganic N at the Xiamen site was 1.62 ± 1.19 mg N L(-1) (n = 46) in 2004-2005 and 1.56 ± 1.39 mg N L(-1) (n = 36) in 2009-2010, although the difference is not significant, nitrate turnover dominates the N component in the latter period. Total deposition flux over Xiamen was 30 kg N ha(-1) yr(-1), of which dry and wet deposition contributed 16% and 84%, respectively. Nitrate in wet deposition with low isotopic value (between -3.05 and -7.48‰) was likely to have mostly originated from combustion NO(x) from vehicle exhausts. The inorganic N in acid deposition exhibited a significant increase (mainly for nitrate) since the mid-1990s, which is consistent with the increased gaseous concentrations of NO(x) and expanding number of automobiles in the coastal city (Xiamen). The time series of nitrate anions and ammonium cations as well as pH values during the period 1990-2009 reflected an increasing trend of N emission with potential implication for N-induced acidification.
The spatial pattern and seasonal variation of denitrification were investigated during 2010-2011 in the Jiulong River Estuary (JRE) in southeast China. Dissolved N? was directly measured by changes in the N?:Ar ratio. The results showed that excess dissolved N? ranged from -9.9 to 76.4 ?mol L?¹. Tidal mixing leads to a seaward decline of dissolved gaseous concentrations and water-air fluxes along the river-estuary gradient. Denitrification at freshwater sites varied between seasons, associated with changes in N input and water temperature. The denitrification process was controlled by the nitrate level at freshwater sites, and the excess dissolved N? observed at the tidal zone largely originated from upstream water transport. Compared to other estuaries, JRE has a relative low gaseous removal efficiency (E(d)=12% of [DIN]; annual N removal=24% of DIN load), a fact ascribed to strong tidal mixing, coarse-textured sediment with shallow depth before bedrock and high riverine DIN input.
Rain storms are predicted to increase in the subtropical region due to climate change. However, the effects of storm events on riverine nitrogen (N) dynamics are poorly understood. In this study, the riverine N dynamics and storm effects in a large subtropical river (North Jiulong River, southeastern China) were investigated through continuous sampling of two storm events which occurred in June 2010 and June 2011. The results disclosed a strong linkage between N dynamics and hydrological controls and watershed characteristics. The extreme storm in June 2010 resulted in more fluctuations in N concentrations, loads, and composition, compared with the moderate storm in June 2011. There were contrasting patterns (e.g., the hysteresis effect) between nitrate and ammonium behavior in storm runoff, reflecting their different supply source and transport mechanism. Overall, nitrate supply originated from subsurface runoff and was dominated by within-channel mobilization, while ammonium was mainly from over-land sources and flushed by surface runoff. Extreme storm runoff (2010) caused a four-fold increase in dissolved inorganic N fluxes (DIN), with a greater fraction of ammonium (up to 30% of DIN) compared with the moderate storm and background flow condition (less than 15%). Storm-driven sharp increases of N loads and changes in nutrient stoichiometry (more ammonium) might have been connected with algal blooms in the adjacent estuary and Xiamen Bay. Combined with the background flow measurement of N gradients along the main river and a stream together with anthropogenic N load information, the interactive effect of hydrological and biogeochemical process on riverine N was preliminarily revealed. Current results suggested that storm runoff N was controlled by rainfall, hydrological condition, antecedent soil moisture, spatial variability of land-based N source, and damming. These findings could be used as a reference for future water quality monitoring programs and the development of a pollution mitigation strategy.
Related JoVE Video
Journal of Visualized Experiments
What is Visualize?
JoVE Visualize is a tool created to match the last 5 years of PubMed publications to methods in JoVE's video library.
How does it work?
We use abstracts found on PubMed and match them to JoVE videos to create a list of 10 to 30 related methods videos.
Video X seems to be unrelated to Abstract Y...
In developing our video relationships, we compare around 5 million PubMed articles to our library of over 4,500 methods videos. In some cases the language used in the PubMed abstracts makes matching that content to a JoVE video difficult. In other cases, there happens not to be any content in our video library that is relevant to the topic of a given abstract. In these cases, our algorithms are trying their best to display videos with relevant content, which can sometimes result in matched videos with only a slight relation.