Transforming growth factor-β (TGF-β) has been shown to play an essential role in the suppression of inflammation, yet recent studies have revealed the positive roles of TGF-β in inflammatory ...responses. For example, TGF-β induces Foxp3-positive regulatory T cells (iTregs) in the presence of interleukin-2 (IL-2), while in the presence of IL-6, it induces pathogenic IL-17 producing Th17 cells. TGF-β inhibits the proliferation of immune cells as well as cytokine production via Foxp3-dependent and -independent mechanisms. Little is known about molecular mechanisms involved in immune suppression via TGF-β; however, Smad2/3 have been shown to play essential roles in Foxp3 induction as well as in IL-2 and IFN-γ suppression, whereas Th17 differentiation is promoted via the Smad-independent pathway. Interaction between TGF-β and other cytokine signaling is important in establishing the balance of immunity and tolerance.
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IZUM, KILJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK
The non-structural carbohydrate (NSC) stored in rice stems (culm plus leaf sheaths) at pre-heading stage is one of the major carbon sources for grain filling. In this study, we conducted field ...experiments in 2018 and 2019 using two varieties, Momiroman (japonica-dominant) and Teqing (indica), which have different accumulation and remobilization patterns of NSC in the stems. We analyzed NSC dynamics of each of the five nodal segments of internodes and leaf sheaths at pre- and post-heading stages. The dynamics of NSC at pre- and post-heading stages differed among segments. The lower segments of internodes and leaf sheaths accumulated more NSC at pre-heading stage compared to the upper segments in both varieties. The lower internodes in Teqing were morphologically larger than in Momiroman and would be able to store more NSC. However, the upper parts of the stems required biomass for development and formation at the stage of NSC accumulation in stems. Momiroman had longer upper internodes and leaf sheaths and required more biomass than Teqing. The NSC remobilization was later in the upper than the lower internodes for both varieties, which led to the delay of NSC remobilization in the entire culm after heading. These results indicated that ideal morphology of stems, to maximize the potential contribution of stem NSC as the carbon source for grain filling, is large lower internodes and short upper internodes and leaf sheaths.
The standard treatment for locally advanced non‐small cell lung cancer (NSCLC) is chemoradiotherapy (CRT) followed by anti‐programmed cell death‐ligand 1 (anti‐PD‐L1) treatment. BIM deletion ...polymorphism induces the suppression of apoptosis resulting from epidermal growth factor (EGFR)‐tyrosine kinase inhibitors in EGFR‐mutated NSCLC patients. We aimed to examine the effects of BIM polymorphism on CRT and anti‐PD‐L1/PD‐1 treatment in NSCLC patients. In this retrospective study of 1312 patients with unresectable NSCLC treated at Higashi‐Hiroshima Medical Center and Hiroshima University Hospital between April 1994 and October 2019, we enrolled those who underwent CRT or chemotherapy using carboplatin + paclitaxel or cisplatin + vinorelbine, or anti‐PD‐L1/PD‐1 treatment. Of 1312 patients, 88, 80, and 74 underwent CRT, chemotherapy, and anti‐PD‐L1/PD‐1 treatment, respectively, and 17.0%, 15.2% and 17.6% of these patients showed BIM polymorphism. Among patients receiving CRT, the progression‐free survival was significantly shorter in those with BIM deletion than in those without. In the multivariate analyses, BIM polymorphism was an independent factor of poor anti‐tumor effects. These results were not observed in the chemotherapy and anti‐PD‐L1/PD‐1 treatment groups. In in vitro experiments, BIM expression suppression using small interfering RNA in NSCLC cell lines showed a significantly suppressed anti‐tumor effect and apoptosis after irradiation but not chemotherapy. In conclusion, we showed that BIM polymorphism was a poor‐predictive factor for anti‐tumor effects in NSCLC patients who underwent CRT, specifically radiotherapy. In the implementation of CRT in patients with BIM polymorphism, we should consider subsequent treatment, keeping in mind that CRT may be insufficient.
We showed that progression‐free survival and overall survival durations were significantly shorter in the CRT‐treated NSCLC patients with BIM polymorphism than in those without. Our findings indicate that BIM polymorphism is associated with the efficacy of radiotherapy but not chemotherapy in patients with CRT.
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SBCE, SBMB, UL, UM, UPUK
Diabetic nephropathy (DN) associated with type 2 diabetes is the most common cause of end-stage renal disease (ESRD) and a serious health issue in the world. Currently, molecular basis for DN has not ...been established and only limited clinical treatments are effective in abating the progression to ESRD associated with DN. Here we found that diabetic
db/db mice which lack the leptin receptor signaling can be used as a model of ESRD associated with DN. We demonstrated that p70S6-kinase was highly activated in mesangial cells in diabetic obese
db/db mice. Furthermore, systemic administration of rapamycin, a specific and potent inhibitor of mTOR, markedly ameliorated pathological changes and renal dysfunctions. Moreover, rapamycin treatment shows a significant reduction in fat deposits and attenuates hyperinsulinemia with few side effects. These results indicate that mTOR activation plays a pivotal role in the development of ESRD and that rapamycin could be an effective therapeutic agent for DN.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK
While it is commonly understood that air temperature can greatly affect the process of photosynthesis and the growth of higher plants, the impact of root zone temperature (RZT) on plant growth, ...metabolism, essential elements, as well as key metabolites like chlorophyll and carotenoids, remains an area that necessitates extensive research. Therefore, this study aimed to investigate the impact of raising the RZT on the growth, metabolites, elements, and proteins of red leaf lettuce. Lettuce was hydroponically grown in a plant factory with artificial light at four different air temperatures (17, 22, 27, and 30°C) and two treatments with different RZTs. The RZT was raised 3°C above the air temperature in one group, while it was not in the other group. Increasing the RZT 3°C above the air temperature improved plant growth and metabolites, including carotenoids, ascorbic acids, and chlorophyll, in all four air temperature treatments. Moreover, raising the RZT increased Mg, K, Fe, Cu, Se, Rb, amino acids, and total soluble proteins in the leaf tissue at all four air temperatures. These results showed that raising the RZT by 3°C improved plant productivity and the metabolites of the hydroponic lettuce by enhancing nutrient uptake and activating the metabolism in the roots at all four air temperatures. Overall, this research demonstrates that plant growth and metabolites can be improved simultaneously with an increased RZT relative to air temperature. This study serves as a foundation for future research on optimizing RZT in relation to air temperature. Further recommended studies include investigating the differential effects of multiple RZT variations relative to air temperature for increased optimization, examining the effects of RZT during nighttime versus daytime, and exploring the impact of stem heating. This research has the potential to make a valuable contribution to the ongoing growth and progress of the plant factory industry and fundamental advancements in root zone physiology. Overall, this research demonstrates that plant growth and metabolites can be improved simultaneously with an increased RZT relative to air temperature. This study serves as a foundation for future research on optimizing RZT in relation to air temperature. Further recommended studies include investigating the differential effects of multiple RZT variations relative to air temperature for increased optimization, examining the effects of RZT during nighttime versus daytime, and exploring the impact of stem heating. This research has the potential to make a valuable contribution to the ongoing growth and progress of the plant factory industry and fundamental advancements in root zone physiology.
Purpose
To propose a new strategy to prevent communication errors caused by unread radiology reports.
Materials and methods
Medical emergencies were prefixed with triple stars on radiology reports, ...and the attending physician was contacted by telephone. Semi-emergencies (medical issues needing addressing within 2 weeks) were prefixed with double stars. Two weeks later, the duty radiologist would search the double-starred reports, and reviewed relevant patient charts to confirm that the information had been appropriately understood and acted upon. If not, the duty radiologist contacted the referral physician by telephone. One year after implementing this strategy, we retrospectively evaluated 1-year worth of data for all the reports of CT, MRI, nuclear medicine and ultrasonography (April 2018 to March 2019).
Results
Three hundred and twenty-one reports were double starred (0.52% of 62,143 reports, 1.32 reports/day), and transmission of relevant information was incomplete in 23 cases (7.17%). Causes of incomplete transmission were (1) reports not being opened (
n
= 17), (2) relevant information on reports being overlooked (
n
= 5), and (3) the wrong report being opened (
n
= 1). Sixty-five reports contained triple stars (0.10%, 0.27 reports/day).
Conclusion
The proposed strategy may be effective in preventing communication errors in radiology reports with important findings requiring semi-emergency clinical action.
Sprouty proteins have been shown to negatively regulate a variety of receptor tyrosine kinase (RTK) signaling pathways and are considered to be tumor suppressor proteins. The pathophysiological ...functions of Sproutys in vivo remain to be investigated. In this study, we examined the physiological function of Sprouty4 as an angiogenic regulator, using Sprouty4 knockout (KO) mice and cells. We found that transplanted tumor cells grow much faster in Sprouty4 KO mice than in wild type (WT) mice, which we associate with enhanced neovascularization in the tumors transplanted into Sprouty4 KO mice. Moreover, vascular endothelial growth factor (VEGF)‐A‐induced angiogenesis and vascular permeability in vivo were enhanced in Sprouty4 KO mice compared with WT mice. Ex vivo angiogenesis, which we induced by VEGF‐A, basic fibroblast growth factor (bFGF), and sphingosine‐1‐phosphate (S1P), was also enhanced in the aortas of Sprouty4 KO mice. We demonstrated that Sprouty4 suppresses Ras‐independent VEGF‐A and S1P signaling, while it does not affect Ras‐dependent VEGF‐C signaling. These data indicate that Sprouty4 selectively suppresses Ras‐independent angiogenic factor signals and is an important negative regulator of pathophysiological angiogenesis. (Cancer Sci 2009; 100: 1648–1654)
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SBCE, SBMB, UL, UM, UPUK
Although transforming growth factor (TGF)-β1 is a well-known immunosuppressive cytokine, little is known about the role of its downstream transcription factors, Smad2 and Smad3, in the suppression of ...macrophage activation. Previous studies have demonstrated that Smad3 is critical for the suppression of LPS-mediated inducible nitric oxide (NO) synthase (iNOS) induction, although the role of Smad2 remains to be investigated. In this study, we found that iNOS induction was enhanced in Smad2-deficient bone marrow-derived macrophages (BMDMs) and peritoneal macrophages in vitro and tumor-associated macrophages in vivo, compared with wild-type (WT) macrophages. However, TGF-β1 still suppressed iNOS induction in Smad2-deficient macrophages. In Smad2/3 double knockout (KO) (Smad2/3 DKO) BMDMs, LPS-mediated NO/iNOS induction was more strongly elevated than in Smad2 or Smad3 single KO BMDMs, and its suppression by exogenous TGF-β1 was severely impaired. These data suggest that Smad2 and Smad3 redundantly regulate iNOS induction. Similarly, the production of IL-6 and TNFα, but not IL-10 was augmented in Smad2/3 DKO BMDMs, suggesting that Smad2 and Smad3 also redundantly suppressed some cytokines production. In Smad2/3 DKO macrophages, TLR3- as well as TLR4-mediated IRF3 activation and IFN-β production were strongly augmented, which resulted in hyper STAT1 phosphorylation. Furthermore, IFN-β- and IFN-γ-induced iNOS induction in the absence of TLR signaling and STAT1 transcriptional activity were augmented in Smad2/3 DKO BMDMs. These results suggest that Smad2 and Smad3 negatively regulate iNOS induction in macrophages by suppressing multiple steps in the IRF3-IFN-β-STAT1 pathway.
Aim
To investigate the association between the use of proton pump inhibitors (PPI) and nosocomial pneumonia and gastrointestinal bleeding in bedridden patients receiving tube feeding.
Methods
A total ...of 116 bedridden hospitalized patients receiving tube feeding, of which 80 were supported by percutaneous endoscopic gastrostomy and 36 by nasogastric tube, were included in the present study. The patients were divided into two groups: 62 patients treated with PPI (PPI group) and 54 patients without PPI (non‐PPI group). Mortality due to nosocomial pneumonia was evaluated using the Kaplan–Meier approach and the log–rank test.
Results
A total of 36 patients (31%) died of nosocomial pneumonia during the observation period; the mortality rate due to nosocomial pneumonia was significantly higher in the PPI group than in the non‐PPI group (P = 0.0395). Cox proportional hazard analysis showed that the use of PPI and lower levels of serum albumin were independent predictors of 2‐year mortality due to nosocomial pneumonia. Gastrointestinal bleeding was observed in four patients in the non‐PPI group (7.7%) and in one patient in the PPI group (1.6%); there was no significant difference between the two groups.
Conclusion
The use of PPI in bedridden tube‐fed patients was independently associated with mortality due to nosocomial pneumonia, and the PPI group had a non‐significant lower incidence of gastrointestinal bleeding than the non‐PPI group. Geriatr Gerontol Int 2018; 18: 1215–1218.
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FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SBCE, SBMB, UL, UM, UPUK
Recurrent chromosomal rearrangements at
BCL11B are found in human hematopoietic malignancies mostly of T-cell origin. However, it is unclear how this disruption contributes to oncogenesis, because ...the majority of leukemias express BCL11B from an undisrupted allele. Here, we show that
Bcl11b
+/−
p53
+/− mice exhibited greater susceptibility to lymphomas than
Bcl11b
+/+
p53
+/− mice but most lymphomas retained and expressed the wild-type
Bcl11b allele. This strongly suggests that
Bcl11b is haploinsufficient for suppression of thymic lymphoma development in mice of the
p53
+/− background, a situation in which functional loss of only one allele confers a selective advantage for tumor growth. The haploinsufficiency is further supported by that
Bcl11b
+/− mouse embryos were impaired in thymocyte development and survival. These results indicate relevance of
BCL11B aberration to human leukemogenesis.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK
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