Antrodia cinnamomea May Interfere with the Interaction Between ACE2 and SARS-CoV-2 Spike Protein in vitro and Reduces Lung Inflammation in a Hamster Model of COVID-19.

Purpose: Coronavirus disease 2019 (COVID-19) poses a global health challenge with widespread transmission. Growing concerns about vaccine side effects, diminishing efficacy, and religious-based hesitancy highlight the need for alternative pharmacological approaches. Our study investigates the impact of the ethanol extract of Antrodia cinnamomea (AC), a native medicinal fungus from Taiwan, on COVID-19 in both in vitro and in vivo contexts. Methods: We measured the mRNA and protein levels of angiotensin-converting enzyme-2 (ACE2) in human lung cells using real-time reverse transcriptase-polymerase chain reaction and Western blotting, respectively. Additionally, we determined the enzymatic activity of ACE2 using the fluorogenic peptide substrate Mca-YVADAPK(Dnp)-OH. To assess the impact of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) infection, we used SARS-CoV-2 pseudovirus infections in human embryonic kidney 293T cells expressing ACE2 to measure infection rates. Furthermore, we evaluated the in vivo efficacy of AC in mitigating COVID-19 by conducting experiments on hamsters infected with the Delta variant of SARS-CoV-2. Results: AC effectively decreased ACE2 mRNA and protein levels, a critical host receptor for the SARS-CoV-2 spike protein, in human lung cells. It also prevented the spike protein from binding to human lung cells. Dehydrosulphurenic acid, an isolate from AC, directly inhibited ACE2 protease activity with an inhibitory constant of 1.53 µM. In vitro experiments showed that both AC and dehydrosulphurenic acid significantly reduced the infection rate of SARS-CoV-2 pseudovirus. In hamsters infected with the Delta variant of SARS-CoV-2, oral administration of AC reduced body weight loss and improved lung injury. Notably, AC also inhibited IL-1ß expression in both macrophages and the lung tissues of SARS-CoV-2-infected hamsters. Conclusion: AC shows potential as a nutraceutical for reducing the risk of SARS-CoV-2 infection by disrupting the interaction between ACE2 and the SARS-CoV-2 spike protein, and for preventing COVID-19-associated lung inflammation.

Fibroblast growth factor 21 reverses high-fat diet-induced impairment of vascular function via the anti-oxidative pathway in ApoE knockout mice.

Circulating endothelial progenitor cells (EPCs), which function in vascular repair, are the markers of endothelial dysfunction and vascular health. Fibroblast growth factor 21 (FGF21), a liver-secreted protein, plays a crucial role in glucose homeostasis and lipid metabolism. FGF21 has been reported to attenuate the progression of atherosclerosis, but its impact on EPCs under high oxidative stress conditions remains unclear. In vitro studies showed that the ß-klotho protein was expressed in cultured EPCs and that its expression was upregulated by FGF21 treatment. Hydrogen peroxide (H2 O2 )-induced oxidative stress impaired EPC function, including cell viability, migration and tube formation. Pretreatment with FGF21 restored the functions of EPCs after the exposure to H2 O2 . Administration of N(ω)-nitro-L-arginine methyl ester (L-NAME), an inhibitor of nitric oxide synthase, inhibited the effects of FGF21 in alleviating oxidative injury by suppressing endothelial nitric oxide synthase (eNOS). In an in vivo study, the administration of FGF21 significantly reduced total cholesterol (TC) and blood glucose levels in apolipoprotein E (ApoE)-deficient mice that were fed a high-fat diet (HFD). Endothelial function, as reflected by acetylcholine-stimulated aortic relaxation, was improved after FGF21 treatment in ApoE-deficient mice. Analysis of mRNA levels in the aorta indicated that FGF21 increased the mRNA expression of eNOS and upregulated the expression of the antioxidant genes superoxide dismutase (SOD)1 and SOD2 in ApoE-deficient mice. These data suggest that FGF21 improves EPC functions via the Akt/eNOS/nitric oxide (NO) pathway and reverses endothelial dysfunction under oxidative stress. Therefore, administration of FGF21 may ameliorate a HFD-induced vascular injury in ApoE-deficient mice.

Synthesis of Asymmetric N-Glycans as Common Core Substrates for Structural Diversification through Selective Enzymatic Glycosylation.

N-glycans on the cell surface provide distinct signatures that are recognized by different glycan-binding proteins (GBPs) and pathogens. Most glycans in humans are asymmetric and isomeric, yet their biological functions are not well understood due to their lack of availability for studies. In this work, we have developed an improved strategy for asymmetric N-glycan assembly and diversification using designed common core substrates prepared chemically for selective enzymatic fucosylation and sialylation. The resulting 26 well-defined glycans that carry the sialic acid residue on different antennae were used in a microarray as a representative application to profile the binding specificity of hemagglutinin (HA) from the avian influenza virus (H5N2). We found distinct binding affinity for the Neu5Ac-Gal epitope linked to the N-acetylglucosamine (GlcNAc) of different branches and only a minor effect in binding for the terminal galactose on different branches. Overall, the microarray analysis showed branch-biased and context-based recognition patterns.

Interaction of mindfulness disposition and instructional self-talk on motor performance: a laboratory exploration.

In considering that high mindfulness disposition individuals possess a unique ability to maintain attention and awareness, and attention is one of the key mechanisms of instructional self-talk, the purpose of this study was to examine the interaction of mindfulness disposition and instructional self-talk on motor performance. Forty-nine college students (M age = 18.96 ± 1.08) with high/low mindfulness disposition (high n = 23; low n = 26) selected out of 126 college students performed a discrete motor task (standing long jump) and a continuous motor task (line tracking task) under instructional and unrelated self-talk conditions. Two separate 2 (self-talk type) X 2 (high/low mindfulness) mixed design ANOVA statistical analyses indicated that mindfulness disposition interacted with unrelated self-talk in the line tracking task. Specifically, low mindfulness participants performed poorer than high mindfulness participants in line tracking task under unrelated self-talk. Further, participants performed better in both standing long jump and line tracking under instructional self-talk than unrelated self-talk. Results not only revealed the triangular relationships among mindfulness, self-talk, and motor performance but also indirectly support the role of attention in self-talk effectiveness. Limitations, future research directions, and practical implications were discussed.

Residues Comprising the Enhanced Aromatic Sequon Influence Protein N-Glycosylation Efficiency.

N-Glycosylation is an important co- and/or post-translational modification that occurs on the vast majority of the one-third of the mammalian proteome that traverses the cellular secretory pathway, regulating glycoprotein folding and functions. Previous studies on the sequence requirements for N-glycosylation have yielded the Asn-X-Ser/Thr (NXS/T) sequon and the enhanced aromatic sequons (Phe-X-Asn-X-Thr and Phe-X-X-Asn-X-Thr), which can be efficiently N-glycosylated. To further investigate the influence of sequence variation on N-glycosylation efficiency in the context of a five-residue enhanced aromatic sequon, we used the human CD2 adhesion domain (hCD2ad) to screen the i-2, i-1, i+1, and i+2 residues flanking Asn at the i position. We found that aromatic residues, especially Trp, and sulfur-containing residues at the i-2 position improved N-glycosylation efficiency, while positively charged residues such as Arg suppressed N-glycosylation. Thiol, hydroxyl, and aliphatic-based side chains at the i-1 position had higher N-glycosylation efficiency, and Cys, in particular, compensated for the negative effect of Arg at the i-2 position. Small residues and Ser at the i+1 position increased the likelihood of N-glycosylation, and Thr is better than Ser at the i+2 position. We devised an algorithm for prediction of N-glycosylation efficiency using the SAS software, employing the 120 sequences studied as a training set. We then introduced the optimized-enhanced aromatic sequons into other glycoproteins and observed an enhancement in N-glycan occupancy that was further supported by modeling the high-affinity interaction between the optimized sequence on hCD2ad and a human oligosaccharyltransferase (OST) subunit. The findings in this study provide useful information for enhancing or suppressing N-glycosylation at a site of interest and valuable data for a better understanding of OST-catalyzed N-glycosylation.

Substrate Preference and Interplay of Fucosyltransferase 8 and N-Acetylglucosaminyltransferases.

The core fucosylation of N-glycans on glycoproteins is catalyzed by fucosyltransferase 8 (FUT8) in mammalian cells and is involved in various biological functions, such as protein function, cancer progression, and postnatal development. The substrate specificity of FUT8 toward bi-antennary N-glycans has been reported, but it is unclear with regard to tri-antennary and tetra-antennary glycans. Here, we examined the specificity and activity of human FUT8 toward tri- and tetra-antennary N-glycans in the forms of glycopeptides. We found that the tri-antennary glycan [A3(2,4,2) type] terminated with N-acetylglucosamine (GlcNAc), which is generated by N-acetylglucosaminyltransferase (GnT)-IV, is a good substrate for FUT8, but the A3(2,2,6) type of tri-antennary glycan, generated by GnT-V, is not a substrate for FUT8. We also observed that core fucosylation reduced the activity of GnT-IV toward the bi-antennary glycan. Examining the correlation between the types of N-glycans and the expression levels of FUT8, GnT-IV, and GnT-V in cells revealed that these glycosyltransferases, particularly GnT-IV, play important roles in directing the branching and core fucosylation of N-glycans in vivo. This study thus provides insights into the interplay among FUT8, GnT-IV, and GnT-V in N-linked glycosylation during the assembly of glycoproteins.

Induction of apoptosis and differentiation by atractylenolide-1 isolated from Atractylodes macrocephala in human leukemia cells.

Atractylodes macrocephula Koidz (A. macrocephula, also known as Baizhu) is an important ingredient in several traditional Chinese herb complexes for the treatment of abdominal pain and gastroenterology diseases for thousands of years. We previously demonstrated the induction of ROS-mediated apoptosis by methanol extract of A. macrocephula in human leukemia cells. After purification and assessment of those active compounds from A. macrocephula ethanol extracts, in this study, we focused on the major active compound, atractylenolide I (ATL-I). Through MTT assay and morphology observation, we found cytotoxic effect of ATL-I in human K562 chronic myeloblastic leukemia (CML), U937 acute myeloblastic leukemia (AML) and Jurkat T lymphoma cells. In addition, ATL-I-induced apoptosis was demonstrated by sub G1 and fragmented chromosomal DNA detection using flow cytometry, enzyme-linked immunosorbent assay (ELISA) and agarose electrophoresis. Finally, we found ATL-I also induced caspase-3 and caspase-9 activation through the detection of procaspase-3, procaspase-9 and caspase-3 substrate poly(ADP-ribose) polymerase (PARP) by immunoblotting. Interestingly, we found that ATL-I induced not only apoptosis but also differentiation, as upregulation of CD14 and CD68 surface markers and increase of phagocytosis ability were discovered in ATL-I-treated K562 CML and U937 AML cells. Our study thus suggests the potential of developing new leukemia therapies by using ATL-I for leukemia treatment in the future.

Galectin-3 Binding Protein and Galectin-1 Interaction in Breast Cancer Cell Aggregation and Metastasis.

Galectin-3 binding protein (Gal-3BP) is a large hyperglycosylated protein that acts as a ligand for several galectins through glycan-dependent interactions. Gal-3BP can induce galectin-mediated tumor cell aggregation to increase the survival of cancer cells in the bloodstream during the metastatic process. However, the galectin interacting with Gal-3BP and its binding specificity has not been identified and structurally elucidated, mainly due to the limitation of mass spectrometry in glycan sequencing. To understand the role of Gal-3BP, we here used liquid chromatography-mass spectrometry combined with specific exoglycosidase reactions to determine the sequences of N-glycans on Gal-3BP from MCF-7 and MDA-MB-231 cells, especially the sequences with terminal sialylation and fucosylation, and addition of LacNAc repeat structures. The N-glycans from both strains are complex type with terminal α2,3-sialidic acid and core fucose linkages, with additional α1,2- and α1,3 fucose linkages found in MCF-7 cells. Compared with that from MCF-7, the Gal-3BP from MDA-MB-231 cells had fewer tetra-antennary structures, only α1,6-linked core fucoses, and more LacNAc repeat structures; the MDA-MB-231 cells had no surface galectin-3 but used surface galectin-1 for interaction with Gal-3BP to form large oligomers and cell aggregates. This study elucidates the specificity of Gal-3BP interacting with galectin-1 and the role of Gal-3BP in cancer cell aggregation and metastasis.

Myocardial Tissue Doppler Imaging Detects Right Ventricular Dysfunction after Percutaneous Angioplasty of Dysfunctional Hemodialysis Access in Uremic Patients.

BACKGROUND: Right ventricular dysfunction has been observed in uremic patients receiving percutaneous transluminal angioplasty (PTA). This prospective study focuses on the impact of tissue Doppler imaging echocardiographic parameters on assessing right ventricle function in uremic patients post PTA of dysfunctional hemodialysis access. METHODS: Sixty uremic patients were divided into two groups by angiographic findings: an occlusive group (26 patients) and a stenotic group (34 patients). All uremic patients underwent routine echocardiography with tissue Doppler imaging both before and immediately following PTA to assess the right ventricular (RV) function and pulmonary artery systolic pressure (PASP). The right ventricular (RV) myocardial performance index (MPI) was obtained during tissue Doppler imaging over the lateral tricuspid annulus. The M index was measured and defined as the peak early diastolic mitral inflow velocity divided by the RV MPI. The RV MPI, RV isovolumic relaxation time (IVRT) and M-index were used to evaluate RV function post-PTA. RESULTS: Immediately following PTA, PASP (31.6 ± 11.3 mmHg versus 42.6 ± 12.0 mmHg, p = 0.001), RV MPI (0.46 ± 0.08 versus 0.62 ± 0.13, p < 0.001) and IVRT (75.1 ± 12.9 versus 98.4 ± 27.7 ms, p < 0.001) increased significantly in the occlusive group. However, PASP and RV function did not change significantly in the stenotic group. In 42.3% patients from the occlusive group, the M-index fell below 112 and RV MPI rose above 0.55 post-PTA; this occurred in only 8.8% of the stenotic group. CONCLUSIONS: This prospective study demonstrated that there was a higher incidence of RV dysfunction in uremic patients with elevated PASP with totally occluded hemodialysis access than those with stenotic access post-PTA. KEY WORDS: Myocardial performance index; Percutaneous transluminal angioplasty; Pulmonary hypertension; Tissue Doppler image; Uremic.

Combining phylogenetic profiling-based and machine learning-based techniques to predict functional related proteins.

Annotating protein functions and linking proteins with similar functions are important in systems biology. The rapid growth rate of newly sequenced genomes calls for the development of computational methods to help experimental techniques. Phylogenetic profiling (PP) is a method that exploits the evolutionary co-occurrence pattern to identify functional related proteins. However, PP-based methods delivered satisfactory performance only on prokaryotes but not on eukaryotes. This study proposed a two-stage framework to predict protein functional linkages, which successfully enhances a PP-based method with machine learning. The experimental results show that the proposed two-stage framework achieved the best overall performance in comparison with three PP-based methods.

Five-Year Outcomes after Acute Myocardial Infarction in Patients with and without Diabetes Mellitus in Taiwan, 1996-2005.

BACKGROUND: Diabetes mellitus (DM) is a strong risk factor of cardiovascular disease. To date, the impact of DM on outcomes after acute myocardial infarction (AMI) in Taiwan is undetermined. The aim of this study was to compare five-year outcomes after AMI in patients with and without diabetes in Taiwan. METHODS: A nationwide cohort of 25,028 diabetic and 56,028 non-diabetic patients who were first hospitalized with AMI between 1996 and 2005 was enrolled through linkage with the Taiwan National Health Insurance research database. Patient mortality rates within 30 days after AMI, and 1, 3, and 5 years thereafter were compared. RESULTS: Length of hospital stay (8.9 ± 8.7 vs. 8.2 ± 8.0 days, p < 0.01) and medical cost during admission (in Taiwan dollars: $129,123 ± $158,073 vs. $121,631 ± $157,018, p < 0.01) were significantly higher in diabetic patients. The difference in mortality rate within 30 days was insignificant between diabetic and non-diabetic patients (18.1% vs. 17.6%, p = 0.06). Mortalities within 1 year (31.0% vs. 26.8%, p < 0.01), 3 years (42.4% vs. 34.7%, p < 0.01), and 5 years (50.6% vs. 41.1%, p < 0.01) were significantly higher in diabetic patients. In patients with AMI who underwent percutaneous coronary intervention (PCI) during index admission, the mortality rate within 30 days was insignificant (6.3% vs. 6.4%, p = 0.70) but mortalities within 1 year (15.2% vs. 11.6%, p < 0.01), 3 years (24.1% vs. 17.2%, p < 0.01), and 5 years (32.2% vs. 22.6%, p < 0.01) were significantly higher in diabetic patients. CONCLUSIONS: The average patient length of hospital stay and medical cost during admission were significantly higher in diabetic patients. Additionally, the difference in mortality rate within 30 days after AMI was insignificant between diabetic and non-diabetic patients. Also, long-term mortality after AMI was significantly higher in diabetic patients. KEY WORDS: Acute myocardial infarction; Diabetes mellitus; Length of hospital stay; Medical cost; Mortality; National health insurance.

Chronic Kidney Disease, But Not Diabetes, Can Predict 30-Day Outcomes in Patients with ST-Elevation Myocardial Infarction after Primary Percutaneous Coronary Intervention: A Single-Center Experience.

BACKGROUND: Patients with acute coronary syndrome and impaired renal function have been shown to have high mortality. However, there is scarce literature to date addressing the impact of diabetes mellitus (DM) and renal function on clinical outcomes of ST elevation myocardial infarction (STEMI) in Taiwan. METHOD: This study enrolled 512 STEMI patients who received primary percutaneous coronary intervention. Patients were divided into 4 groups including group 1: patients without DM or CKD (nDM-nCKD); group 2: patients with DM but without CKD (DM-nCKD); group 3: patients with CKD but without DM (nDM-CKD); group 4: patients with DM and CKD (DM-CKD). Patients were also classified into four groups based on their estimated glomerular filtration rates (eGFR): stage 1 (eGFR ≥ 90 ml/min/1.73 m(2), n = 163), stage 2 (eGFR = 89-60 ml/min/1.73 m(2), n = 171), stage 3 (eGFR = 59-30 ml/min/1.73 m(2), n = 136), and stage 4 (eGFR < 30 ml/min/1.73 m(2), n = 42). The complication rates, length of hospital stay, and 30-day outcomes were analyzed. RESULTS: The patients in both the nDM-CKD group and DM-CKD group had higher incidences of hypotension, intra-aortic balloon counterpulsation use, and respiratory failure (p < 0.005). They had significantly longer hospital stay and 30-day mortality rates (p < 0.001). The patients with CKD stage 3 and 4 had longer hospital stay and higher 30-day mortality rates (p < 0.001). However, DM was not an independent factor on the length of hospital stay and 30-day mortality rates. CONCLUSIONS: STEMI patients with impaired renal function, but not DM, had significantly longer hospital stay and higher 30-day mortality rates. KEY WORDS: Chronic kidney disease; Diabetes mellitus; Mortality; Primary percutaneous coronary intervention; ST-segment elevation myocardial infarction.

The Effect of Intensified Low Density Lipoprotein Cholesterol Reduction on Recurrent Myocardial Infarction and Cardiovascular Mortality.

BACKGROUND: Lipid-lowering therapy plays an important role in preventing the recurrence of cardiovascular events in patients after acute myocardial infarction (AMI). This study aimed to assess the effect of intensified low density lipoprotein cholesterol (LDL-C) reduction on recurrent myocardial infarction and cardiovascular mortality in patients after AMI. METHOD: The 562 enrolled AMI patients (84.2% male) were divided into two groups according to 3-month LDL-C decrease percentage equal to or more than 40% (n = 165) and less than 40% (n = 397). To evaluate the long-term efficacy of LDL-C reduction, the 5-year outcomes were collected, including time to the first occurrence of myocardial infarction and time to cardiovascular death. RESULTS: The baseline characteristics and complication rates were not different between the two study groups. The patients with 3-month LDL-C decrease ≥ 40% had higher baseline LDL-C and lower 3-month, 1-year, 2-year, 3-year, 4-year and 5-year LDL-C than the patients with 3-month LDL-C decrease < 40%. In Kaplan-Meier analyses, those patients with 3-month LDL-C decrease ≥ 40% had a higher rate of freedom from myocardial infarction (p = 0.006) and survival rate (p = 0.02) at 5-year follow-up. The 3-month LDL-C < 40% parameter was significantly related to cardiovascular death (HR: 9.62, 95% CI 1.18-78.62, p < 0.04). CONCLUSIONS: After acute myocardial infarction, 3-month LDL-C decrease < 40% was identified to be a significant risk factor for predicting 5-year cardiovascular death. The patients with 3-month LDL-C decrease ≥ 40% had a higher rate of freedom from myocardial infarction and lower cardiovascular mortality, even though these patients had higher baseline LDL-C value. KEY WORDS: Acute myocardial infarction; Cardiovascular death; Low-density lipoprotein cholesterol; Mortality; Statin.

Soyasaponin I decreases the expression of alpha2,3-linked sialic acid on the cell surface and suppresses the metastatic potential of B16F10 melanoma cells.

The transfer of sialic acids to the non-reducing terminal positions on sugar chains of glycoconjugates is catalyzed by sialyltransferases (STs). Increased sialylation is correlated with oncogenic transformation and metastatic potential. ST inhibitors may be potentially valuable as anti-cancer and anti-metastatic agents. In this study, we evaluated the effects of soyasaponin I (Ssa I), a known inhibitor of STs, on tumor metastasis through studying a highly metastatic cancer cell line B16F10. Ssa I specifically inhibited the expression of alpha2,3-linked sialic acids without affecting other glycans on the B16F10 cell surface. We also found that Ssa I decreased the migratory ability of cells, enhanced cell adhesion to extracellular matrix proteins. Finally, a pulmonary metastasis assay demonstrated that alteration of glycosylation in this way significantly reduced the ability of tumor cells to distribute to the lungs of mice. Collectively, these findings suggested that alpha2,3-linked sialic acids may play an important role in metastasis potential of B16F10 cells.

Comparison of real-time contrast echocardiography and low-dose dobutamine stress echocardiography in predicting the left ventricular functional recovery in patients after acute myocardial infarction under different therapeutic intervention.

BACKGROUND: Early prediction of left ventricular (LV) functional recovery after acute myocardial infarction (AMI) remains challenging. This prospective study aims to compare real-time myocardial contrast echocardiography (MCE) with low-dose dobutamine stress echocardiography (LDDSE) in predicting the LV functional recovery in patients after AMI who underwent different therapeutic interventions. METHODS: Ninety-two patients with AMI were divided into 3 groups: primary coronary intervention group (n=34), thrombolysis group (n=30) and conservative therapy group (n=28). MCE was performed 2.3+/-0.7 days after chest pain onset. LDDSE was done within 2 days of MCE study. Follow-up echocardiography was performed 4 months later. RESULTS: Patients treated by primary coronary intervention or thrombolysis had significantly lower regional perfusion score (0.65+/-0.53 vs. 1.01+/-0.49, p=0.008; 0.78+/-0.55 vs. 1.01+/-0.49, p=0.03), better contractile reserve (regional dobutamine Deltawall motion score -1.12+/-0.39 vs. -0.80+/-0.43, p=0.01; -0.99+/-0.50 vs. -0.80+/-0.43, p=0.08) and LV function recovery (regional Deltawall motion score -1.67+/-0.53 vs. -1.02+/-0.46, p=0.003; -1.42+/-0.58 vs. -1.02+/-0.46, p=0.03) than those of conservative therapy group. MCE and LDDSE showed good concordance for predicting LV functional recovery (kappa=0.63, p<0.001). Perfusion score index had a good correlation with LV functional recovery (r=-0.75, p<0.001). CONCLUSIONS: This study demonstrates that perfusion score index obtained from real-time MCE is comparable to LDDSE in predicting the LV functional recovery even under different therapeutic interventions. Revascularization results in better preservation of myocardial microvascular integrity, regional contractile reserve and LV functional recovery.

Stachybotrydial, a potent inhibitor of fucosyltransferase and sialyltransferase.

Elevated expression of fucosylated glycoconjugates and fucosyltransferases (Fuc-Ts) is found in various tumor cells and has been correlated with aspects of tumor progression such as cell adhesion and metastasis. Thus, fucosyltransferase inhibitors are potentially useful as anti-tumor agents. In the present study, three known spirocyclic drimanes (1, 2, and 3) were isolated from the culture broth of the fungus Stachybotrys cylindrospora. Compound 1 (stachybotrydial) exhibits potent inhibitory activity against alpha1,3-fucosyltransferase (Fuc-TV) during screening, while compounds 2 and 3 show no such inhibitory activity. Kinetic analysis indicates that compound 1 is an uncompetitive inhibitor with respect to GDP-fucose and a noncompetitive inhibitor with respect to N-acetyllactosamine with Ki values of 10.7 and 9.7 microM, respectively. In addition, all three compounds also possess inhibitory activity against sialyltransferase (ST) but not against beta1,4-galactosyltransferase. These observations provide novel chemical structure information that will help in the design of novel Fuc-T and ST inhibitors.

Soyasaponin-I-modified invasive behavior of cancer by changing cell surface sialic acids.

OBJECTIVE: Sialylation involving tumor formation and invasive behavior goes along with altered sialyltransferase (ST) activity. A potent ST inhibitor, soyasaponin I (SsaI), was discovered to selectively inhibit the cellular alpha2,3-sialyltranserase activity. In this study, we further test the effects of SsaI on modifying the metastatic and invasive behaviors of cancer cell lines. METHODS: Nonmetastatic breast cancer cell line, MCF-7, and highly metastastic breast cancer cell line, MDA-MB-231, were used to investigate the effects of SsaI on tumor cells. RESULTS: SsaI did not affect cell growth cycle and also failed to inhibit cell growth in this study (the concentration of SsaI < or=100 muM). SsaI was as predicted to successfully inhibit cellular alpha2,3-ST activity and depressed the dose-dependent tumor cell surface alpha2,3-sialic acid expression. In addition, different concentrations of SsaI did stimulate MCF-7 cell adhesion to collagen type I linearly and significantly enhanced cell adhesion to the Matrigel-matrix. Furthermore, SsaI significantly decreased MDA-MB-231 cell migration. Reverse transcriptase polymerase chain reaction for evaluating mRNA expression of ST3Gal I, III and IV showed that SsaI also down-regulated the expression of ST3Gal IV but did not affect the other two. CONCLUSIONS: The results showed that SsaI was implicated in the invasive behavior of tumor cells, suggesting that altered alpha2,3-sialylation pathway played a crucial role in the adhesion and tumor metastases. SsaI is a good candidate for studying the biological roles of ST, and might provide a new preventive strategy in tumor metastasis.

Catheter-associated urinary tract infections in intensive care units can be reduced by prompting physicians to remove unnecessary catheters.

OBJECTIVE: Indwelling urinary catheters are the most common source of infections in intensive care units (ICUs). The aim of this study was to evaluate the efficacy of nurse-generated daily reminders to physicians to remove unnecessary urinary catheters 5 days after insertion. DESIGN: A time-sequence nonrandomized intervention study. SETTING: Adult ICUs (medical, surgical, cardiovascular surgical, neurosurgical, and coronary care) of a tertiary-care university medical center. PATIENTS: All patients admitted to the adult ICUs during a 2-year period. The study consisted of a 12-month observational phase (15,960 patient-days) followed by a 12-month intervention phase (15,525 patient-days). INTERVENTION: Daily reminders to physicians from the nursing staff to remove unnecessary urinary catheters 5 days after insertion. RESULTS: The duration of urinary catheterization was significantly reduced during the intervention phase (from 7.0 + 1.1 days to 4.6 +/- 0.7 days; P < .001). The rate of catheter-associated urinary tract infection (CAUTI) was also significantly reduced (from 11.5 +/- 3.1 to 8.3 +/- 2.5 patients with CAUTI per 1,000 catheter-days; P = .009). There was a linear relationship between the monthly average duration of catheterization and the rate of CAUTI (r = 0.50; P = .01). The excess monthly cost of antibiotics for CAUTI was reduced by 69% (from 4021 dollars +/- 1800 dollars to 1220 dollars +/- 941 dollars; P = .004). CONCLUSION: This study demonstrated that a simple measure instituted as part of a continuous quality improvement program significantly reduced the duration of urinary catheterization, rate of CAUTI, and additional costs of antibiotics to manage CAUTI.