Blocking of intracellular ROS production by phytoglycoprotein (30 kDa) causes anti-proliferation in bisphenol A-stimulated Chang liver cells

Dioscorea batatas Decne (DBD) is traditionally used to heal inflammatory disease as a folk medicine. It was reported that a glycoprotein (DBD glycoprotein) with a molecular weight of 30 kDa was isolated from DBD and consists of carbohydrate (83.75%) and protein (16.25%) moieties. The previous results showed that it has a strong scavenging activity against hydroxyl radicals without any pro-oxidant activity in the cell-free system. The purpose of the present study was to show whether or not the DBD glycoprotein inhibits cell proliferation-related signal transduction stimulated by bisphenol A (BPA, an environmental hormone) in Chang liver cells. The results in this study indicated that DBD glycoprotein (200 microg ml(-1)) has suppressive effects on abnormal cell viability, production of intracellular reactive oxygen species (ROS) and nitric oxide (NO) in BPA (50 microM)-induced Chang liver cells by blocking the phosphorylation of mitogen-activated protein kinase (MAPK) and activating protein-1 (AP-1) activity. In addition, DBD glycoprotein (200 microg ml(-1)) normalized the activity of catalase (CAT) and glutathione peroxidase (GPx). Consequently, DBD glycoprotein inhibits the expression of proliferating cell nuclear antigen (PCNA, cell proliferation maker) stimulated by BPA. Therefore, it is speculated that DBD glycoprotein protects against carcinogenic events caused by BPA in Chang liver cells.     

Selectively targeting estrogen receptors for cancer treatment

Estrogens regulate growth and development through the action of two distinct estrogen receptors (ERs), ERα and ERβ, which mediate proliferation and differentiation of cells. For decades, ERα mediated estrogen signaling has been therapeutically targeted to treat breast cancer, most notably with the selective estrogen receptor modulator (SERM) tamoxifen. Selectively targeting ERs occurs at two levels: tissue selectivity and receptor subtype selectivity. SERMs have been developed with emphasis on tissue selectivity to target ER signaling for breast cancer treatment. Additionally, new approaches to selectively target the action of ERα going beyond ligand-dependent activity are under current investigation. As evidence of the anti-proliferative role of ERβ accumulates, selectively targeting ERβ is an attractive approach for designing new cancer therapies with the emphasis shifted to designing ligands with subtype selectivity. This review will present the mechanistic and structural features of ERs that determine tissue and subtype selectivity with an emphasis on current approaches to selectively target ERα and ERβ for cancer treatment.     

Summary of Spanish recommendations on intensive care to facilitate organ donation

With the aim of consolidating recommendations about the practice of initiating or continuing intensive care to facilitate organ donation (ICOD), an ad hoc working group was established, comprising 10 intensivists designated by the Spanish Society of Intensive Care and Coronary Units (SEMICYUC) and the Spanish National Transplant Organization (ONT). Consensus was reached in all recommendations through a deliberative process. After a public consultation, the final recommendations were institutionally adopted by SEMICYUC, ONT, and the Transplant Committee of the National Health‐Care System. This article reports on the resulting recommendations on ICOD for patients with a devastating brain injury for whom the decision has been made not to apply any medical or surgical treatment with a curative purpose on the grounds of futility. Emphasis is made on the systematic referral of these patients to donor coordinators, the proper assessment of the likelihood of brain death and medical suitability, and on transparency in communication with the patient′s family. The legal and ethical aspects of ICOD are addressed. ICOD is considered a legitimate practice that offers more patients the opportunity of donating their organs upon their death and helps to increase the availability of organs for transplantation.     

基于有效组分检测与理化表征相结合的当归补血汤制备工艺与质量控制研究

目的优选当归补血汤的制备工艺,探索以理化表征参数作为汤剂制备工艺评价与质量控制手段的可行性。方法采用正交试验设计,主要以有效组分阿魏酸、黄芪甲苷、黄芪皂苷、多糖的量为指标,全面考察当归补血汤的制备工艺,并对所得提取液进行流变学、表面化学、电化学等方面的表征,将表征参数与组分的量进行多项式回归分析。结果优选的当归补血汤制备工艺条件为取处方药材加12倍量水,提取3次,每次1.0 h;理化表征显示,不同制备工艺条件所得汤剂理化参数差别较大,且渗透压与体系组分的量关系最为密切,表面张力、电导率次之,而pH值、黏度与体系组分的量关系不密切。结论初步表明,表面张力、电导率和渗透压可作为当归补血汤制备工艺与质量控制的评价指标,通过提取液的理化表征来进行质量控制具有一定的可行性。     

Portrayal of Brain Death in Film and Television

We sought to evaluate whether television and cinematic coverage of brain death is educational or misleading. We identified 24 accessible productions that addressed brain death using the archives of the Paley Center for Media (160 000 titles) and the Internet Movie Database (3.7 million titles). Productions were reviewed by two board‐certified neurologists. Although 19 characters were pronounced brain dead, no productions demonstrated a complete examination to assess for brain death (6 included an assessment for coma, 9 included an evaluation of at least 1 brainstem reflex, but none included an assessment of every brainstem reflex, and 2 included an apnea test). Subjectively, both authors believed only a small fraction of productions (13% A.L., 13% J.W.) provided the public a complete and accurate understanding of brain death. Organ donation was addressed in 17 productions (71%), but both reviewers felt that the discussions about organ donation were professional in a paucity of productions (9% for A.L., 27% for J.W.). Because television and movies serve as a key source for public education, the quality of productions that feature brain death must be improved.     

Anti-inflammatory activity of bark of Dioscorea batatas DECNE through the inhibition of iNOS and COX-2 expressions in RAW264.7 cells via NF-κB and ERK1/2 inactivation

We identified a bioactive herbal medicine with anti-inflammatory activity from an ethanol extract derived from the bark of Dioscorea batatas DECNE (BDB) in RAW264.7 cells. We examined the effects of BDB on nitric oxide (NO) and prostaglandin E₂ (PGE₂) production in LPS-induced RAW264.7 cells. BDB consistently inhibited both NO and PGE₂ production in a dose-dependent manner, with an IC₅₀ of 87–71 μg/ml, respectively. The reduction of NO and PGE₂ production were accompanied by a reduction in iNOS and COX-2 protein expression, as evaluated by Western blotting. To evaluate the action mode of BDB and its ability to inhibit iNOS and COX-2 protein expression, we assessed the effects of BDB on nuclear factor-κB (NF-κB) DNA-binding activity, NF-κB-dependent reporter gene activity, inhibitory factor-κB (IκB) phosphorylation and degradation, and p65 nuclear translocation. BDB suppressed DNA-binding activity and reporter gene activity as well as translocation of the NF-κB p65 subunit. BDB also down-regulated IκB kinase (IKK), thus inhibiting LPS-induced both phosphorylation and the degradation of IκBα. In addition, BDB also inhibited the LPS-induced activation of ERK1/2.     

Transplanting kidneys from donation after cardiac death donors with acute kidney injury

Donation after cardiac death (DCD) and acute kidney injury (AKI) donors have historically been considered independent risk factors for delayed graft function (DGF), allograft failure, and inferior outcomes. With growing experience, updated analyses have shown good outcomes. There continues to be limited data, however, on outcomes specific to DCD donors who have AKI. Primary outcomes for this study were post–kidney transplant patient and allograft survival comparing two donor groups: DCD AKIN stage 2‐3 and DBD AKIN stage 2‐3. In comparing these groups, there were no short‐ or long‐term differences in patient (hazard ratio [HR] 1.07, 95% confidence interval [CI] 0.54‐1.93, P = .83) or allograft survival (HR 1.47, 95% CI 0.64‐2.97, P = .32). In multivariate models, the DCD/DBD status had no significant impact on the estimated GFR (eGFR) at 1 (P = .38), 2 (P = .60), and 3 years (P = .52). DGF (57.9% vs 67.9%, P = .09), rejection (12.1% vs 13.9%, P = .12), and progression of interstitial fibrosis/tubular atrophy (IFTA) on protocol biopsy (P = .16) were similar between the two groups. With careful selection, good outcomes can be achieved utilizing severe AKI DCD kidneys. Historic concerns regarding primary nonfunction, DGF resulting in interstitial fibrosis and rejection, and inferior outcomes were not observed. Given the ongoing organ shortage, increased effort should be undertaken to further utilize these donors.