Polymeric monolithic columns based on natural wood for rapid purification of targeted protein.

With multiscale hierarchical structure, wood is suitable for a range of high-value applications, especially as a chromatographic matrix. Here, we have aimed to provide a weak anion-exchange polymeric monolithic column based on natural wood with high permeability and stability for effectively separating the targeted protein. The wood-polymeric monolithic column was synthesized by in situ polymerization of glycidyl methacrylate and ethylene glycol dimethacrylate in wood, and coupled with diethylaminoethyl hydrochloride. The wood-polymeric monolithic column can be integrated with fast-protein liquid chromatography for large-scale protein purification. According to the results, the wood-polymeric monolithic column showed high hydrophilicity, permeability and stability. Separation experiments verified that the wood-polymeric monolithic column could purify the targeted protein (spike protein of SARS-COV-2 and ovalbumin) from the mixed proteins by ion exchange, and the static adsorption capacity was 33.04 mg mL-1 and the dynamic adsorption capacity was 24.51 mg mL-1. In addition, the wood-polymerized monolithic column had good stability, and a negligible decrease in the dynamic adsorption capacity after 20 cycles. This wood-polymerized monolithic column can provide a novel, efficient, and green matrix for monolithic chromatographic columns.

Bioinspired and biomimetic strategies for inflammatory bowel disease therapy.

Inflammatory bowel disease (IBD) is an idiopathic chronic inflammatory bowel disease with high morbidity and an increased risk of cancer or death, resulting in a heavy societal medical burden. While current treatment modalities have been successful in achieving long-term remission and reducing the risk of complications, IBD remains incurable. Nanomedicine has the potential to address the high toxic side effects and low efficacy in IBD treatment. However, synthesized nanomedicines typically exhibit some degree of immune rejection, off-target effects, and a poor ability to cross biological barriers, limiting the development of clinical applications. The emergence of bionic materials and bionic technologies has reshaped the landscape in novel pharmaceutical fields. Biomimetic drug-delivery systems can effectively improve biocompatibility and reduce immunogenicity. Some bioinspired strategies can mimic specific components, targets or immune mechanisms in pathological processes to produce targeting effects for precise disease control. This article highlights recent research on bioinspired and biomimetic strategies for the treatment of IBD and discusses the challenges and future directions in the field to advance the treatment of IBD.

Bioinspired Heterogeneous Construction of Lignocellulose-Reinforced COF Membranes for Efficient Proton Conduction.

The exponential interest in covalent organic frameworks (COFs) arises from the direct correlation between their diverse and intriguing properties and the modular design principle. However, the insufficient interlamellar interaction among COF nanosheets greatly hinders the formation of defect-free membranes. Therefore, developing a methodology for the facile fabrication of these materials remains an enticing and highly desirable objective. Herein, ultrahigh proton conductivity and superior stability are achieved by taking advantage of COF composite membranes where 2D TB-COF nanosheets are linked by 1D lignocellulosic nanofibrils (LCNFs) through π-π and electrostatic interactions to form a robust and ordered structure. Notably, the high concentration of -SO3 H groups within the COF pores and the abundant proton transport paths at COFs-LCNFs interfaces impart composite membranes ultrahigh proton conductivity (0.348 S cm-1 at 80 °C and 100% RH). Moreover, the directional migration of protons along the stacked nanochannels of COFs is facilitated by oxygen atoms on the keto groups, as demonstrated by density functional theory (DFT) calculations. The simple design concept and reliable operation of the demonstrated mixed-dimensional composite membrane are expected to provide an ideal platform for next-generation conductive materials.

Examined lymph node numbers influence prognosis in rectal cancer treated with neoadjuvant therapy.

Background: The number of lymph nodes examined (LNe) is often insufficient in patients with rectal cancer (RC) treated with neoadjuvant therapy; however, its prognostic value remains controversial. Thus, we retrospectively explored whether LNe had an influence on staging and prognosis and investigated whether there was a cut-off value for better prognosis in patients with RC treated with neoadjuvant therapy. Methods: Data were collected from seven prospective hospital databases in China from July 2002 to May 2018. Binary logistic regression models were used to predict lymph node metastasis. The cut-off value for LNe was determined using X-tile 3.6.1. Survival outcomes and risk factors were analyzed using the log-rank test and Cox regression model. Results: A total of 482 patients were included, of whom 459 had complete overall survival (OS) information. Using the percentile method, the total number of lymph nodes examined (TLNe) was 14-16 (40th-60th percentile), and the proportion of patients with lymph node metastasis reached a maximum of 48.1%. Cox multivariate analysis showed that the odds ratio (OR) remained the highest when TLNe was 14-16 (OR = 3.379, P = 0.003). The 3-year and 5-year OS were 85.4% and 77.8%, respectively. Negative lymph nodes examined (NLNe) of ≤6 was an independent risk factor for 3-year and 5-year OS (3-year OS 71.1% vs. 85.9%, P = 0.004; 5-year OS 66.3% vs. 74.3%, P = 0.035). Subgroup analysis for patients with ypN + showed that higher 3-year and 5-year OS were achieved when the TLNe was >10, 78.8% vs. 54.0% (P = 0.005), and 60.8% vs. 36.0% (P = 0.012), respectively. Patients with ypN0M0 had a higher 5-year OS when the TLNe was >19 (P = 0.055). Conclusion: The TLNe and NLNe influenced the staging accuracy and demonstrated prognostic value in patients with RC treated with neoadjuvant therapy.

Rational engineering of adeno-associated virus capsid enhances human hepatocyte tropism and reduces immunogenicity.

OBJECTIVES: Gene therapy based on recombinant adeno-associated viral (rAAV) vectors has been proved to be clinically effective for genetic diseases. However, there are still some limitations, including possible safety concerns for high dose delivery and a decreasing number of target patients caused by the high prevalence of pre-existing neutralizing antibodies, hindering its application. Herein, we explored whether there was an engineering strategy that can obtain mutants with enhanced transduction efficiency coupled with reduced immunogenicity. METHODS: We described a new strategy for AAV capsids engineering by combining alterations of N-linked glycosylation and the mutation of PLA2-like motif. With this combined strategy, we generated novel variants derived from AAV8 and AAVS3. RESULTS: The variants mediated higher transduction efficiency in human liver carcinoma cell lines and human primary hepatocytes as well as other human tissue cell lines. Importantly, all the variants screened out showed lower sensitivity to neutralizing antibody in vitro and in vivo. Moreover, the in vivo antibody profiles of variants were different from their parental AAV capsids. CONCLUSIONS: Our work proposed a new combined engineering strategy and engineered two liver-tropic AAVs. We also obtained several AAV variants with a higher transduction efficiency and lower sensitivity of neutralizing antibodies. By expanding the gene delivery toolbox, these variants may further facilitate the success of AAV gene therapy.

Comprehensive analysis of the glutathione S-transferase Mu (GSTM) gene family in ovarian cancer identifies prognostic and expression significance.

Background: Ovarian cancer (OC) is one of the most common types of gynecologic tumor over the world. The Glutathione S-transferase Mu (GSTM) has five members, including GSTM1-5. These GSTMs is involved in cell metabolism and detoxification, but their role in OC remains unknown. Methods: Data from multiple public databases associated with OC and GSTMs were collected. Expression, prognosis, function enrichment, immune infiltration, stemness index, and drug sensitivity analysis was utilized to identify the roles of GSTMs in OC progression. RT-qPCR analysis confirmed the effect of AICAR, AT-7519, PHA-793887 and PI-103 on the mRNA levels of GSTM3/4. Results: GSTM1-5 were decreased in OC samples compared to normal ovary samples. GSTM1/5 were positively correlated with OC prognosis, but GSTM3 was negatively correlated with OC prognosis. Function enrichment analysis indicated GSTMs were involved in glutathione metabolism, drug metabolism, and drug resistance. Immune infiltration analysis indicated GSTM2/3/4 promoted immune escape in OC. GSTM5 was significantly correlated with OC stemness index. GSTM3/4 were remarkedly associated with OC chemoresistance, especially in AICAR, AT-7519, PHA-793887 and PI-103. Conclusion: GSTM3 was negatively correlated with OC prognosis, and associated with OC chemoresistance and immune escape. This gene may serve as potential prognostic biomarkers and therapeutic target for OC patients.

[LAMTOR2 deficiency exacerbates Klebsiella pneumoniae-induced liver sepsis in mice].

Objective To explore the biological function and mechanisms of LAMTOR2 during Klebsiella pneumoniae(K. pneumoniae) induced liver sepsis by establishing late endosomal/lysosomal adaptor 2(LAMTOR2) gene liver conditional knockout mouse model infected by K. pneumoniae. Methods LAMTOR2 gene liver conditional knockout mice (LAMTOR2flox/flox; Alb-Cre+) and littermate controls (LAMTOR2flox/flox) were generated and bred. LAMTOR2 gene knockout efficiency in liver was determined by real-time quantitative PCR (RT-qPCR) and Western blot analysis. Then, both group mice were infected with K. pneumoniae, and survival rates and liver pathological changes were determined. The expression levels of liver TNF-α, IL-1ß and CXCL1 mRNA were detected by RT-qPCR. Results LAMTOR2 gene liver conditional knockout mice were generated and bred successfully; compared to the littermate controls, LAMTOR2flox/flox, Alb-Cre+ mice showed lower survival rates and more severe liver injury. The expression levels of TNF-α, IL-1ß and CXCL1 mRNA were reduced in LAMTOR2flox/flox and the ability of immune response was decreased in mice. Alb-Cre+ mice liver compared to these of littermate controls post K. pneumoniae infections. Conclusion LAMTOR2 plays a protective role during K. pneumoniae-induced liver sepsis.

Diagnostic performance of DCE-MRI, multiparametric MRI and multimodality imaging for discrimination of breast non-mass-like enhancement lesions.

OBJECTIVE: The aim of this study was to investigate and compare the diagnostic performance of dynamic contrast-enhanced (DCE)-MRI, multiparametric MRI (mpMRI), and multimodality imaging (MMI) combining mpMRI and mammography (MG) for discriminating breast non-mass-like enhancement (NME) lesions. METHODS: This retrospective study enrolled 193 patients with 199 lesions who underwent 3.0 T MRI and MG from January 2017 to December 2019. The features of DCE-MRI, turbo inversion recovery magnitude (TIRM), and diffusion-weighted imaging (DWI) were assessed by two breast radiologists. Then, all lesions were divided into microcalcification and non-microcalcification groups to assess the features of MG. Comparisons were performed between groups using univariate analyses. Then, multivariate analyses were performed to construct diagnostic models for distinguishing NME lesions. Diagnostic performance was evaluated by using the area under the curve (AUC) and the differences between AUCs were evaluated by using the DeLong test. RESULTS: Overall (n = 199), mpMRI outperformed DCE-MRI alone (AUCmpMRI = 0.924 vs. AUCDCE-MRI = 0.884; p = 0.007). Furthermore, MMI outperformed both mpMRI and MG (the microcalcification group [n = 140]: AUCMMI = 0.997 vs. AUCmpMRI = 0.978, p = 0.018 and AUCMMI = 0.997 vs. AUCMG = 0.912, p < 0.001; the non-microcalcification group [n = 59]: AUCMMI = 0.857 vs. AUCmpMRI = 0.768, p = 0.044 and AUCMMI = 0.857 vs. AUCMG = 0.759, p = 0.039). CONCLUSION & ADVANCES IN KNOWLEDGE: DCE-MRI combined with DWI and TIRM information could improve the diagnostic performance for discriminating NME lesions compared with DCE-MRI alone. Furthermore, MMI combining mpMRI and MG showed better discrimination than both mpMRI and MG.

An Asia-specific variant of human IgG1 represses colorectal tumorigenesis by shaping the tumor microenvironment.

Emerging studies have focused on ways to treat cancers by modulating T cell activation. However, whether B cell receptor signaling in the tumor microenvironment (TME) can be harnessed for immunotherapy is unclear. Here, we report that an Asia-specific variant of human IgG1 containing a Gly396 to Arg396 substitution (hIgG1-G396R) conferred improved survival of patients with colorectal cancer (CRC). Mice with knockin of the murine functional homolog mIgG2c-G400R recapitulated the alleviated tumorigenesis and progression in murine colon carcinoma models. Immune profiling of the TME revealed broad mobilizations of IgG1+ plasma cells, CD8+ T cells, CD103+ DCs, and active tertiary lymphoid structure formation, suggesting an effective antitumor microenvironment in hIgG1-G396R CRC patients. Mechanistically, this variant potentiated tumor-associated antigen-specific (TAA-specific) plasma cell differentiation and thus antibody production. These elevated TAA-specific IgG2c antibodies in turn efficiently boosted the antibody-dependent tumor cell phagocytosis and TAA presentation to effector CD8+ T cells. Notably, adoptive transfer of TAA-specific class-switched memory B cells harboring this variant exhibited therapeutic efficacy in murine tumor models, indicating their clinical potential. All these results prompted a prospective investigation of hIgG1-G396R in patients with CRC as a biomarker for clinical prognosis and demonstrated that manipulating the functionality of IgG1+ memory B cells in tumors could improve immunotherapy outcomes.

Enhanced proton conductivity of Nafion membrane induced by incorporation of MOF-anchored 3D microspheres: a superior and promising membrane for fuel cell applications.

A novel 3D core-shell material composed of polyacrylate carboxyl microspheres (PCMs) and ZIF-8 nanoparticles was used to promote proton conduction in the Nafion matrix. The Nafion/ZIF-8@PCM membranes displayed excellent proton conductivity (0.24 S cm-1) and physicochemical properties due to special structural characteristics. More importantly, this new concept has a strong practical guiding significance for the fabrication of novel PEMs.

A novel green lignosulfonic acid/Nafion composite membrane with reduced cost and enhanced thermal stability.

A green biopolymer, lignosulfonate acid (LSA), was first used as an additive in the Nafion membrane for fuel cell applications. The Nafion/LSA composite membrane displayed enhanced thermal stability and other satisfactory properties due to the stable aromatic groups and multiple active sites of LSA. More importantly, the cost-effectiveness and simple fabrication of such novel composite PEMs make their use in PEMFCs very attractive and economical.

Self-Assembled pH-Sensitive Nanoparticles Based on Ganoderma lucidum Polysaccharide-Methotrexate Conjugates for the Co-delivery of Anti-tumor Drugs.

In tumor therapy, polymer nanoparticles are ideal drug delivery materials because they can mask the disadvantages of anti-tumor drugs such as poor solubility in water, high toxicity, and side effects. However, most polymer-based nanoparticles do not themselves have anti-tumor properties. Herein, a novel pH-sensitive nanoparticle drug delivery system based on Ganoderma lucidum polysaccharides (GLPs), which have demonstrated anti-tumor activities, was designed to enable the delivery of methotrexate (MTX) and 10-hydroxycamptothecin (HCPT) to tumor cells, where they could exert synergistic anti-tumor effects. The prepared nanoparticles were irregularly spherical in shape with a uniform particle size of ∼190 nm, and they exhibited a high drug-loading capacity (MTX 21.5% and HCPT 22.6%) and excellent biocompatibility. Moreover, the loaded MTX and HCPT units were rapidly released under acidic conditions within the tumor cells while remaining stable under normal physiological conditions. Meanwhile, compared to free MTX and HCPT, the GLP-APBA-MTX/HCPT nanoparticles presented exhibited better tumor suppressive effects and fewer side effects in vivo, which indicates that they may be an effective anti-tumor treatment strategy.

Effect of continuous nursing combined with salcatonin on postoperative pains in elderly patients after hip replacement.

OBJECTIVE: This study was designed to explore the effect of continuous nursing combined with salcatonin on the improvements of postoperative pain in elderly patients after hip replacement. METHODS: A total of 99 elderly patients treated by hip replacement in our hospital were divided into the control group (CG, n=49, routine nursing + salcatonin) and the study group (SG, n=50, continuous nursing + salcatonin). The visual analogue scale (VAS) during rest (RVAS), VAS during initiative movement (IVAS) and VAS during passive movement = (PVAS) at 3 d, 7 d, 10 d, 14 d and 30 d after operation, the Harris hip score (HHS), Barthel index and geriatric depression scale (GDS) at 1 month after operation, and the incidences of tumble and refracture during the postoperative 6-month follow-up were compared between the two groups. RESULTS: In comparison with the CG, except for higher HHS and Barthel index at 1 month after operation (P<0.05), the SG was associated with lower RVAS, IVAS and PVAS at 7 d, 10 d, 14 d and 30 d after operation (P<0.05), lower GDS at 1 month after operation, and lower incidences of tumble and refracture during the 6 months after operation (P<0.05). CONCLUSION: The combination of continuous nursing and salcatonin has achieved marked effects not only on mitigating the pains at the early stage after a hip replacement in elderly patients, but also on improving their joint functions and reducing the incidences of tumble and refracture in a long run.

lncRNA GAS5 Is Upregulated in Osteoporosis and Downregulates miR-21 to Promote Apoptosis of Osteoclasts.

BACKGROUND: It has been reported that lncRNA growth arrest-specific transcript 5 (GAS5) interacts with miR-21, which plays critical roles in osteoporosis. The involvement of GAS5 in osteoporosis was investigated in this study. METHODS: Expression levels of GAS5 and miR-21 in plasma of both osteoporosis patients and healthy controls were determined by RT-qPCR. Diagnostic values of GAS5 and miR-21 for osteoporosis were analyzed by ROC curve analysis. Overexpression experiments were used to assess the interactions between GAS5 and miR-21. The roles of GAS5 and miR-21 in the apoptosis of osteoclasts were investigated by cell apoptosis assay. RESULTS: The present study aimed to investigate the roles of GAS5 in osteoporosis. The results showed that GAS5 was upregulated, while miR-21 was downregulated in plasma of osteoporosis patients. Expression levels of GAS5 and miR-21 were inversely correlated across plasma samples from osteoporosis patients but not the plasma samples from the controls. Altered expression of GAS5 and miR-21 distinguished osteoporosis patients from the controls. In osteoclasts, overexpression of GAS5 led to downregulation of miR-21, while overexpression of miR-21 did not affect the expression of GAS5. Overexpression of GAS5 led to promoted apoptosis of osteoclasts, while overexpression of miR-21 led to suppressed apoptosis of osteoclasts. In addition, overexpression of miR-21 attenuated the enhancing effects of overexpressing GAS5 on cell apoptosis. CONCLUSION: GAS5 is upregulated in osteoporosis and may downregulate miR-21 to promote the apoptosis of osteoclasts.

Multicenter study of surgical and oncologic outcomes of extra-levator versus conventional abdominoperineal excision for lower rectal cancer.

BACKGROUND: The surgical and oncological outcome of extra-levator abdominoperineal excision (ELAPE) procedure remains unclear in low rectal cancer. METHODS: A total of 194 cases of rectal cancer patients underwent ELAPE or conventional abdominoperineal excision (APE) procedure were analyzed in four hospitals' databases from January 2010 to December 2015. Clinicopathological data, overall survival (OS), disease free survival (DFS) and local recurrence free survival (LRFS) of patients were compared between two groups. RESULTS: The operation time spent in perineal phase was significantly shorter in the ELAPE group than that in conventional APE procedure (P < 0.001). There were more specimens with excellent or good quality in ELAPE group compared to conventional APE group (P = 0.033). Patients whom underwent ELAPE procedures showed significantly better OS, DFS and LRFS than those underwent conventional APE procedures. Patients with preoperative stage cT3∼T4 (P = 0.033, P = 0.008, P = 0,033), cN+ (P = 0.002, P < 0.001, P = 0.006) and pathological stage III-IV (P = 0.023, P = 0.008, P = 0.016) were associated with significant benefits from ELAPE procedure in terms of OS, DFS and LRFS. DFS differed significantly between two groups of patients whom got preoperative chemoradiation therapy (P = 0.009) or postoperative chemotherapy (P = 0.029). For patients of pathological stage IIII-IV without preoperative chemoradiation, ELAPE procedures resulted in statistically better OS (P = 0.018) and DFS (P = 0.030). ELAPE procedure was an independent risk factor of OS, DFS and LRFS in multivariate analysis. CONCLUSION: Low rectal cancer patients might benefit from ELAPE procedure on both surgical and oncological outcomes, especially in patients with relatively advanced tumors, inspite of the effects of pre-operative radio- and chemotherapy.

[Investigation of Lung Cancer Patients Complicated with Chronic Obstructive Pulmonary Disease in Thoracic Surgical Department].

BACKGROUND: Lung cancer is an important complication of chronic obstructive pulmonary disease (COPD), and even significantly affects the prognosis of patients with COPD. COPD also affects the postoperative complications and recurrence in patients with lung cancer. This study aims to investigate lung cancer patients complicated with COPD in thoracic surgical department. METHODS: All medical records of lung cancer patients discharged from the Department of Thoracic Surgery of People's Hospital, Peking University during January 2015 and December 2015 were reviewed, including gender, age, tobacco smoke history, harmful occupational exposure, clinic symptom, chest computed tomography (CT) scanning, postoperative pathology result report, discharged diagnosis and spirometry [All patients underwent pulmonary function test are received bronchial dilation test if the based predicted value of forced expiratory volume in one second (FEV1) <70%]. RESULTS: A full set of lung function test was measured in 703 lung cancer patients. Bronchial dilation test was finished in 67 patients. 62 (92.5%) patients were diagnosed as COPD. 677 cases with lung cancer were received surgery. Bronchial dilation test was measured in 42 cases. Of them 38 (92.7%) patients were diagnosed as COPD. It was found that the patients with lung cancer and COPD was more frequent in males, elders (≥65 yr), smokers, non-adenocarcinoma patients than those of patients without COPD (P<0.05). The males and the elders (≥65 yr) were more likely to suffer from COPD (OR: 2.374-2.807, 95%CI: 1.101-7.157)(P<0.05). Only 3 patients (4.3‰) were diagnosed as COPD and received standard treatment before admission. And only 5 patients (7.1‰) were diagnosed as COPD as discharged. CONCLUSIONS: The routine pulmonary function as well as bronchial dilation test are helpful for screening the patients with COPD. At present, the diagnosis and treatment of lung cancer combined with COPD is a serious problem, which needs to be paid attention to by thoracic surgeons and to join hands with physicians in order to improve the diagnosis level of COPD.

[Corrigendum] Jumonji AT-rich interactive domain 1B overexpression is associated with the development and progression of glioma.

Following the publication of the article, the authors noted that there were certain errors in the data and presentation of some of the parts of the figures. The correct images are shown below. [the original article was published in the International Journal of Molecular Medicine 38: 172-182, 2016; DOI: 10.3892/ijmm.2016.2614].

Jumonji AT-rich interactive domain 1B overexpression is associated with the development and progression of glioma.

Previous studies have suggested that jumonji AT-rich interactive domain 1B (JARID1B) plays an important role in the genesis of some types of cancer, and it is therefore considered to be an important drug target protein. Although the expression of JARID1B has been researched in some types of cancer, little is known about JARID1B expression in glioma and its function in the tumorigenesis of gliomas. In the present study, we examined the expression of JARID1B in glioma. In addition, RT-PCR, western blot analysis and immunohistochemical analysis were performed using glioma tissue samples and the results revealed that JARID1B expression increased according to the histological grade of glioma. However, in the normal brain tissue samples JARID1B expression was barely detected. Kaplan­Meier analysis revealed that higher JARID1B expression in patients with glioma was associated with a poorer prognosis. The overexpression of JARID1B stimulated the proliferation and migration of glioma cells as well as sphere formation, whereas suppressing the expression of JARID1B produced opposite effects. The overexpression of JARID1B increased the tumorigenicity of glioma cells in vivo in a nude mouse xenograft model of glioma. Moreover, the activation of phosphorylated (p-)Smad2 contributes to JARID1B-induced oncogenic activities. These findings suggest that JARID1B is involved in the pathogenesis of glioma, and that the downregulation of JARID1B in glioma cells may be a therapeutic target for the treatment of patients with glioma.

Propofol-induced Inhibition of Catecholamine Release Is Reversed by Maintaining Calcium Influx.

BACKGROUND: Propofol (2,6-diisopropylphenol) is one of the most frequently used anesthetic agents. One of the main side effects of propofol is to reduce blood pressure, which is thought to occur by inhibiting the release of catecholamines from sympathetic neurons. Here, the authors hypothesized that propofol-induced hypotension is not simply the result of suppression of the release mechanisms for catecholamines. METHODS: The authors simultaneously compared the effects of propofol on the release of norepinephrine triggered by high K-induced depolarization, as well as ionomycin, by using neuroendocrine PC12 cells and synaptosomes. Ionomycin, a Ca ionophore, directly induces Ca influx, thus bypassing the effect of ion channel modulation by propofol. RESULTS: Propofol decreased depolarization (high K)-triggered norepinephrine release, whereas it increased ionomycin-triggered release from both PC12 cells and synaptosomes. The propofol (30 µM)-induced increase in norepinephrine release triggered by ionomycin was dependent on both the presence and the concentration of extracellular Ca (0.3 to 10 mM; n = 6). The enhancement of norepinephrine release by propofol was observed in all tested concentrations of ionomycin (0.1 to 5 µM; n = 6). CONCLUSIONS: Propofol at clinically relevant concentrations promotes the catecholamine release as long as Ca influx is supported. This unexpected finding will allow for a better understanding in preventing propofol-induced hypotension.

Kruppel-like factor 4 is a novel mediator of selenium in growth inhibition.

A previous prevention trial showed that selenium supplementation was effective in reducing (by 50%) the incidence of prostate cancer. Selenium has been reported to inhibit the growth of prostate cancer cells in vitro. Multiple mechanisms are likely to be operative in the underlying effect of selenium. Here, we report that Krüppel-like factor 4 (KLF4), a transcription factor of the KLF family, is an important target of selenium. We found that selenium up-regulates KLF4 expression and increases the DNA-binding activity of KLF4 in both the androgen-dependent LNCaP and the androgen-independent PC-3 human prostate cancer cells. The increase of KLF4 mRNA is accounted for primarily by enhanced transcription, although the contribution of a slight abatement in mRNA degradation cannot be ruled out. KLF4 knockdown using short interference RNA significantly weakens the effects of selenium on DNA synthesis inhibition, apoptosis induction, and the expression of three KLF4 target genes, cyclin D1, p21/WAF1, and p27/Kip1. In addition, the overexpression of KLF4 not only leads to an induction of apoptosis in the control cells, but also enhances the DNA synthesis-suppressive and-proapoptotic activities of selenium. Taken together, our results suggest that KLF4 plays a key role in mediating the growth-inhibitory effect of selenium in prostate cancer cells.