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Abstract: Rice (Oryza sativa), an important cereal as a staple food worldwide, can be used in gluten-free diets. This study aimed to isolate and characterize the active rice proteins and assess the anti-leukaemia response via in vitro and ex vivo experiments. Temperature-stable protein-containing extracts augmented this effect. Proteomic analysis identified various protein spots known with functions involving metabolism-related, transport, storage, antioxidation, development, and disease-resistance proteins. Among these, storage proteins were the most abundant. To avoid masking the other relatively scanty rice storage proteins, albumin, globulin, glutelin and prolamin were separated and quantified. The human peripheral blood mononuclear cells-conditioned medium (PBMC-CM) prepared from prolamin treatment showed an increment in production of tumor necrosis factor-α. Human leukaemia U937 cells cultured in the presence of prolamin-prepared PBMC-CM were inhibited in growth capacity and were triggered differentiation toward monocytes. Neutralization of prolamin by polyclonal antibody attenuated its activity. Rice prolamin, undetectable by wheat gliadin-specific antibody, has greater anti-leukaemia activity than wheat proteins glutenin and gliadin. In conclusion, rice prolamin is effective in activating human anti-leukaemia immunity and may not induce unwanted inflammatory diseases. [Copyright &y& Elsevier]

Abstract: The 77 residue propeptide at the N-terminal end of subtilisin E plays an essential role in subtilisin folding as a tailor-made intramolecular chaperone. Upon completion of folding, the propeptide is autoprocessed and removed by subtilisin digestion. This propeptide-mediated protein folding has been used as a paradigm for the study of protein folding. Here, we show by three independent methods, that the propeptide domain and the subtilisin domain show distinctive intrinsic stability that is obligatory for efficient autoprocessing of the propeptide domain. Two tryptophan residues, Trp106 and Trp113, on the surface of subtilisin located on one of the two helices that form the interface between the propeptide and the subtilisin domains play a key role in maintaining the distinctive instability of the propeptide domain, after completion of folding. When either of the Trp residues was substituted with Tyr, the characteristic biphasic heat denaturation profile of two domains unfolding was not observed, resulting in a single transition of denaturation. The results provide evidence that the propeptide not only plays an essential role in subtilisin folding, but upon completion of folding it behaves as an independent domain. Once the propeptide-mediated folding is completed, the propeptide domain is readily eliminated without interference from the subtilisin domain. This “autotomic” behavior of the propeptide may be a prevailing principle in propeptide-mediated protein folding. [Copyright &y& Elsevier]

Objectives A previous study has suggested the benefit of sub-renal vein radiotherapy (SRVRT) for pelvic lymph node (PLN)-positive cervical cancer. In order to better select patients for SRVRT, this study aimed to evaluate the value of a risk-based radiation field based on PLN location and number in PLN-positive cervical cancer. Methods We reviewed 198 patients with FIGO stage IB2–IVA cervical cancer, positive PLNs, and negative para-aortic lymph nodes (PALNs) from 2004 to 2015 at two tertiary centers. All patients underwent pelvic radiotherapy (PRT) or SRVRT with IMRT. The SRVRT extended the PRT field cranially to the level of the left renal vein. The prescribed doses were 45–50.4 Gy in 1.8 Gy per fraction. Results Overall, 118 and 80 patients underwent PRT and SRVRT, respectively. The SRVRT group had more advanced disease based on FIGO stage, common iliac PLNs, and number of PLNs. The median follow-up was 63 months (range: 7–151 months). PALN failure was experienced by 28 patients (23.7%) in the PRT group and 1 patient (1.3%) in the SRVRT group ( p < 0.001). Compared with PRT, SRVRT significantly improved 5-year PALN recurrence-free survival (56.8% vs. 100%, p < 0.001) and cancer-specific survival (56.5% vs. 93.9%, p < 0.001) among patients with common iliac PLNs or ≥ 3 PLNs. No significant differences were observed in these outcomes among patients with PLNs below the common iliac bifurcation and 1–2 PLNs. The SRVRT did not increase severe toxicities. Conclusions Risk-based radiation field based on PLN location and number could optimize outcomes for PLN-positive cervical cancer. [ABSTRACT FROM AUTHOR]

Objective To evaluate the effects of prophylactic sub-renal vein radiotherapy (SRVRT) using intensity-modulated radiotherapy (IMRT) for cervical cancer. Methods A total of 206 patients with FIGO stage IB2–IVA cervical cancer and negative para-aortic lymph nodes (PALNs) who underwent pelvic IMRT (PRT) or SRVRT between 2004 and 2013 at our institution were reviewed. SRVRT cranially extended the PRT field for PALNs up to the left renal vein level. The prescribed dose was consistent 50.4 Gy in 28 fractions. Results Overall, 110 and 96 patients underwent PRT and SRVRT, respectively. The SRVRT group had more advanced disease based on FIGO stage and positive pelvic lymph nodes (PLNs). The median follow-up time was 60 months (range, 7–143). For the total study population, the 5-year PALN recurrence-free survival (PARFS) and overall survival (OS) for PRT vs. SRVRT were 87.6% vs. 97.9% ( p = 0.03) and 74.5% vs. 87.8% ( p = 0.04), respectively. In patients with FIGO III–IVA or positive PLNs, the 5-year PARFS and OS for PRT vs. SRVRT were 80.1% vs. 96.4% ( p = 0.02) and 58.1% vs. 83.5% ( p = 0.012), respectively. However, there were no significant differences in these outcomes for patients with FIGO IB–IIB and negative PLNs. In a multivariate analysis, only SRVRT was associated with better PARFS (HR, 0.21; 95% CI, 0.06–0.78; p = 0.02). The SRVRT did not significantly increase severe late toxicities. Conclusion Prophylactic SRVRT using IMRT reduced PALN recurrence with tolerable toxicities, supporting the application of risk-based radiation fields for cervical cancer. [ABSTRACT FROM AUTHOR]

Background: Platonin is an immunomodulator with NF-κB inhibitory activity. It not only inhibits interleukin (IL)-1β, IL-6, and tumor necrosis factor (TNF)-α production in sepsis, but also attenuates heatstroke reactions. In addition, platonin redirects differentiation of dendritic cells toward an intermediate stage of maturation. The study was designed to examine whether platonin can reduce acute graft rejection. Materials and Methods: A C57BL/6 to BALB/c mice skin transplantation model was used. Platonin was given intraperitoneally to transplant recipients at various doses. Skin grafts were submitted to histologic analysis. NF-κB DNA binding activity and inducible nitric oxide synthase (iNOS) expression were determined in harvested draining lymph nodes. Leukocyte count, hepatic and renal functions were serially assessed. An array of serum cytokines was evaluated on d 1, 3, 5, and 7 after skin transplantation. Results: Platonin resulted in significantly prolonged skin allograft survival in a dose- and time-dependent manner. Histologic changes in the skin allografts paralleled the gross appearance of rejection. Serum cytokine analysis shows that platonin significantly suppressed the production of the proinflammatory cytokines IL-6 and TNF-α. However, no significant changes occurred in the serum levels of Th1-type and Th2-type cytokines. NF-κB activity and iNOS expression were remarkably suppressed in draining lymph nodes. In terms of toxicity, there were no significant differences in body weight, leukocyte count, plasma alanine aminotransferase, or creatinine between the platonin-treated and control groups. Conclusion: Platonin effectively prolongs skin allograft survival without major toxicity. [ABSTRACT FROM AUTHOR]

Background: Dendritic cells (DCs) play a central role in both stimulating and suppressing immune responses and are impacted by surgical injury, exercise, and other physiological stressors. This study aims to determine whether renal ischemia/reperfusion (I/R) injury alters the differentiation, maturation, and activation of DCs from peripheral blood monocytes (PBMo). Materials and methods: Sprague-Dawley (SD) rats were subjected to I/R injury or sham-operated. Creatinine clearance (CCr) was monitored daily during the 14 days of reperfusion that followed the ischemic insult. At 2 and 14 days of reperfusion, the following properties of PBMo derived-DCs were assessed: the amount of generated DCs, surface markers [CD11c, CD80, CD86, and MHC-II (IA)], and functional status including magnitude of mixed lymphocyte reaction (MLR), production of IL-12 p70 by DCs, and production of IFN-γ and IL-4 by DC-stimulated T cells. Results: CCr was greatly reduced in the injured rats 0 to 4 days after ischemia. Two days after I/R injury to kidney, the numbers of DCs differentiated from PBMo, IL-12 production by DCs, expression of MHC-II (IA), and IFN-γ production by DC-stimulated T cells were significantly increased in the I/R injured group (compared to the sham-operated group). After 14 days of reperfusion, there was no between-group differences in the numbers of DCs derived from PBMo, MLR, expression of CD80, CD86, and MHC-II (IA), and production of IL-12, IFN-γ, and IL-4. Conclusions: The increases seen at 2 days of reperfusion may reflect a preparatory step in the renal I/R injury pathway. The relationship between up-regulation of DC differentiation and ischemic acute renal failure (ARF) remains to be elucidated. [Copyright &y& Elsevier]

• EFLA 945, a product of red grape vine leaf extracts attenuate the AIM2 inflammasome. • EFLA 945 interferes with the entry of extracellular DNA into the cells. • EFLA 945 attenuates imiquimod-induced psoriasis in mouse model. • EFLA 945 attenuates imiquimod-induced inflammatory responses in psoriatic skin. Psoriasis is a chronic inflammatory skin disease that affects about 2% of the general population. Activation of the Absent in Melanoma 2 (AIM2) inflammasome is crucial for immune defense, but it can also cause inflammatory and autoimmune diseases, including psoriasis. We currently lack an AIM2 inflammasome inhibitor that could be used therapeutically. Here, we show that EFLA 945, a safe product of red grape vine leaf extracts, can restrict AIM2 inflammasome activation. Mechanistically, EFLA945 prevents DNA entry into THP-1-derived macrophages, and thereby inhibits cytoplasmic DNA-dependent apoptosis-associated speck-like protein containing a CARD (ASC) oligomerization, caspase-1 activation, and the secretion of interleukin (IL)-1β and IL-18. The major phytochemicals of EFLA 945, resveratrol and peonidin 3-O-glucoside (P3G), appear to be the potential bioactive compounds responsible for its ability to restrict AIM2-dependent IL-1β secretion. Importantly, in an in vivo mouse model, EFLA 945 attenuates imiquimod (IMQ)-induced psoriasis-related pro-inflammatory responses in topical psoriatic skin, including caspase-1 activation, IL-1β maturation, and IL-17 production, and decreases the severity of psoriasis. Together, these results demonstrate that the safe natural product, EFLA 945, can restrict the AIM2 inflammasome activation through preventing DNA entry and may prove beneficial for treating psoriasis. [ABSTRACT FROM AUTHOR]