Protective Effect of Resveratrol Combined with Levodopa Against Oxidative Damage in Dopaminergic Neurons.

Levodopa (L-3,4-dihydroxyphenylalanine, L-Dopa) alleviates the symptoms of Parkinson's disease (PD), yet prolonged usage may give rise to severe adverse effects. Resveratrol (RSV) is a potent antioxidant, anticancer and anti-inflammatory agent. And a variety of polyphenol antioxidant compounds derived from RSV combined with levodopa have demonstrated neuroprotective activity against neuronal cell death. The purpose of this study was to examine the impact of this combination of RSV and L-Dopa on the survival rate, growth status, and reactive oxygen species (ROS) of MES23.5 dopamine (DA) neuron cells. In this study, we induced MPP+ in MES23.5 dopamine neuron cells and observed their survival rate, growth status, ROS content, as well as the effect of RSV combined with L-Dopa on cell survival. We also measured malondialdehyde (MDA) levels and superoxide dismutase (SOD) activity levels as indicators of mitochondrial function, oxidative stress, and oxidative damage in the cells. Our results indicated that the MES23.5 dopamine neurons had decreased survival, poor growth status, and increased ROS content after MPP+ induction. Moreover, we found that MDA levels were elevated, and SOD activity levels were decreased, suggesting that the cells experienced abnormal mitochondrial function. However, when RSV was combined with L-Dopa, the cells showed a reduced level of MPP + -induced oxidative damage, with a more significant inhibitory effect observed in the RSV group at a concentration of 50 µmol/L. In conclusion, we found that the effects of co-administration of RSV with L-Dopa (100 µmol/L) was more effective than L-Dopa administered at the high dose. Thus, we found that RSV has the potential to reduce the dose of L-Dopa required to improve PD symptoms.

Effect of ATG8 or SAC1 deficiency on the cell proliferation and lifespan of the long-lived PMT1 deficiency yeast cells.

Autophagy is pivotal in maintaining intracellular homeostasis, which involves various biological processes, including cellular senescence and lifespan modulation. Being an important member of the protein O-mannosyltransferase (PMT) family of enzymes, Pmt1p deficiency can significantly extend the replicative lifespan (RLS) of yeast cells through an endoplasmic reticulum (ER) unfolded protein response (UPR) pathway, which is participated in protein homeostasis. Nevertheless, the mechanisms that Pmt1p regulates the lifespan of yeast cells still need to be explored. In this study, we found that the long-lived PMT1 deficiency strain (pmt1Δ) elevated the expression levels of most autophagy-related genes, the expression levels of total GFP-Atg8 fusion protein and free GFP protein compared with wild-type yeast strain (BY4742). Moreover, the long-lived pmt1Δ strain showed the greater dot-signal accumulation from GFP-Atg8 fusion protein in the vacuole lumen through a confocal microscope. However, deficiency of SAC1 or ATG8, two essential components of the autophagy process, decreased the cell proliferation ability of the long-lived pmt1Δ yeast cells, and prevented the lifespan extension. In addition, our findings demonstrated that overexpression of ATG8 had no potential effect on the RLS of the pmt1Δ yeast cells, and the maintained incubation of minimal synthetic medium lacking nitrogen (SD-N medium as starvation-induced autophagy) inhibited the cell proliferation ability of the pmt1Δ yeast cells with the culture time, and blocked the lifespan extension, especially in the SD-N medium cultured for 15 days. Our results suggest that the long-lived pmt1Δ strain enhances the basal autophagy activity, while deficiency of SAC1 or ATG8 decreases the cell proliferation ability and shortens the RLS of the long-lived pmt1Δ yeast cells. Moreover, the maintained starvation-induced autophagy impairs extension of the long-lived pmt1Δ yeast cells, and even leads to the cell death.

Cascade electrocatalysis via AgCu single-atom alloy and Ag nanoparticles in CO2 electroreduction toward multicarbon products.

Electrocatalytic CO2 reduction into value-added multicarbon products offers a means to close the anthropogenic carbon cycle using renewable electricity. However, the unsatisfactory catalytic selectivity for multicarbon products severely hinders the practical application of this technology. In this paper, we report a cascade AgCu single-atom and nanoparticle electrocatalyst, in which Ag nanoparticles produce CO and AgCu single-atom alloys promote C-C coupling kinetics. As a result, a Faradaic efficiency (FE) of 94 ± 4% toward multicarbon products is achieved with the as-prepared AgCu single-atom and nanoparticle catalyst under ~720 mA cm-2 working current density at -0.65 V in a flow cell with alkaline electrolyte. Density functional theory calculations further demonstrate that the high multicarbon product selectivity results from cooperation between AgCu single-atom alloys and Ag nanoparticles, wherein the Ag single-atom doping of Cu nanoparticles increases the adsorption energy of *CO on Cu sites due to the asymmetric bonding of the Cu atom to the adjacent Ag atom with a compressive strain.

The Ethanol Extract of Evodiae Fructus and Its Ingredient, Rutaecarpine, Inhibit Infection of SARS-CoV-2 and Inflammatory Responses.

COVID-19, derived from SARS-CoV-2, has resulted in millions of deaths and caused unprecedented socioeconomic damage since its outbreak in 2019. Although the vaccines developed against SARS-CoV-2 provide some protection, they have unexpected side effects in some people. Furthermore, new viral mutations reduce the effectiveness of the current vaccines. Thus, there is still an urgent need to develop potent non-vaccine therapeutics against this infectious disease. We recently established a series of detecting platforms to screen a large library of Chinese medicinal herbs and phytochemicals. Here, we reveal that the ethanolic extract of Evodiae Fructus and one of its components, rutaecarpine, showed promising potency in inhibiting the activity of 3C-like (3CL) protease, blocking the entry of the pseudo-typed SARS-CoV-2 (including wild-type and omicron) into cultured cells. In addition, inflammatory responses induced by pseudo-typed SARS-CoV-2 were markedly reduced by Evodiae Fructus extract and rutaecarpine. Together our data indicate that the herbal extract of Evodiae Fructus and rutaecarpine are potent anti-SARS-CoV-2 agents, which might be considered as a treatment against COVID-19 in clinical applications.

Capsaicin, a Phytochemical From Chili Pepper, Alleviates the Ultraviolet Irradiation-Induced Decline of Collagen in Dermal Fibroblast via Blocking the Generation of Reactive Oxygen Species.

Capsaicin, a major ingredient in chili pepper, has broad pharmaceutical applications, including relieving pain, anti-inflammation, and treating psoriasis. In dermatological biology, capsaicin has been shown to prevent the ultraviolet (UV)-induced melanogenesis via TRPV1 receptor. To strengthen the roles of capsaicin in skin function, the damaged skin, triggered by exposure to UV, was reversed by capsaicin in both in vitro and in vivo models. In cultured dermal fibroblasts, the exposure to UV induced a decrease of collagen synthesis and increases expression of matrix metalloproteinases (MMPs), generation of reactive oxygen species (ROS), and phosphorylation of Erk and c-Jun, and these events subsequently led to skin damage. However, the UV-mediated damages could be reversed by pre-treatment with capsaicin in a dose-dependent manner. The effect of capsaicin in blocking the UV-mediated collagen synthesis was mediated by reducing generation of ROS in dermal fibroblasts, instead of the receptor for capsaicin. Hence, capsaicin has high potential value in applying as an agent for anti-skin aging in dermatology.

Decreased IL-37 expression in hepatocellular carcinoma tissues and liver cancer cell lines.

The role of IL-37 in cancer is currently largely unknown. The present study aimed to investigate IL-37 expression in hepatocellular carcinoma (HCC), paracancerous tissues (PT) and liver cancer cell lines, and their associations between IL-37 and NF-κB. A total of 65 HCC and 65 PT tissues were collected. The expression of IL-37 and NF-κB in tissues was detected by immunohistochemistry (IHC) and the data was analyzed using SPSS software. In the in vitro studies, IL-37 gene was transfected into HepG2 and MHCC97H cell lines with Lipofectamine 3000, and the protein regulation of NF-κB by IL-37 was verified by immunofluorescence (IF) and western blotting. In HCC, the positive expression rates of IL-37 and NF-kB were 21.5 and 95.4%, respectively. In PT, strong positive staining of IL-37and weak positive staining of NF-κB were observed. The normal expression levels of IL-37 and NF-κB, the increased IL-37 and decreased NF-κB induced by IL-37 gene transfection were observed through IF in cell lines. In terms of clinical significance, the difference in IL-37 expression between HCC and PT was statistically significant (χ2=55.05; P<0.001). IL-37 expression in HCC but not PT was negatively associated with serum AFP (χ2=6.522; P=0.039). IL-37 expression in PT was associated with sex (χ2=13.12; P=0.003) and tumor size (χ2=7.996; P=0.045). NF-κB expression in PT was associated with age, sex and BCLC stage. Notably, there was a negative correlation between IL-37 and NF-κB in HCC (r=-0.277; P=0.029) but not in PT (P>0.05). IL-37 overexpression downregulated the NF-κB protein by 56.50% in HepG2 cells (P<0.05) and 30.52% in MHCC97H cells (P<0.05). In conclusion, the expression of IL-37 in HCC and PT was specifically associated with serum AFP and tumor size, respectively. IL-37 expression was negatively correlated with NF-κB protein expression in HCC tissues and liver cancer cell lines.

Low expression of IL-37 protein is correlated with high Oct4 protein expression in hepatocellular carcinoma.

OBJECTIVE: The function of IL-37 in cancer remains largely unclear. The present research was to probe the protein expression of IL-37 and Oct4 in hepatocellular carcinoma (HCC), para-cancerous tissues (PT) and cancer cell lines, and discuss their relationship. METHODS: Forty-nine HCC specimens and forty-nine PT samples were collected for immunohistochemical staining of IL-37 and Oct4 protein. Then, the correlations among IL-37, Oct4 and the clinical indicators were analyzed. In further in vitro studies, IL-37 was over expressed in HepG2 and MHCC97H cancer cell lines by gene transfection using a lipo3000 kit. Finally, the protein expression of IL-37 and Oct4 was detected by immunofluorescence and western blot to verify the in vivo correlation between IL and 37 and Oct4. RESULTS: In HCC, IL-37 protein expression was weakly positive with a positive rate of 12.2% while Oct4 expression was strongly positive with a positive rate of 91.8%. In PT, strong positive IL-37 (83.7%) and weakly positive Oct4 (91.8%) were shown. The increased IL-37 and decreased Oct4 induced by IL-37 gene transfection were observed through IF in cells. In terms of clinical significance, the difference of IL-37 expression between HCC and PT was statistically significant (χ2 = 51.815, P = 3.2796 × 10-11). IL-37 in tumor tissues was associated with serum AFP (χ2 = 5.515, P = 0.048) and cirrhosis (χ2 = 7.451, P = 0.014). IL-37 expression of PT was link to gender (χ2 = 10.376, P = 0.013) and tumor size (χ2 = 8.118, P = 0.04). The expression of Oct4 in HCC was related to the patient's gender and cirrhosis. Importantly, there was a negative correlation between IL and 37 and Oct4 in tumor tissues (r = -0.299, P = 0.047) but not in PT (P > 0.05). Oct4 protein expression was down-regulated by IL-37 by 63.35% in HepG2 cells (P < 0.05) and 95.20% in MHCC97H cells (P < 0.05). CONCLUSION: IL-37 expression in tumor tissues and PT was related to serum AFP and liver cirrhosis, tumor size, respectively. IL-37 protein expression was correlated with Oct4 in cancer cell lines and tumor tissues but not PT. The present study indicated that IL-37 might play a role in the development of HCC.

IL-37 promotes cell apoptosis in cervical cancer involving Bim upregulation.

Background: Growing evidence has indicated that interleukin-37 (IL-37) is a potential anticancer molecule that mainly plays an inhibiting role in different kinds of cancers, but data for the role of IL-37 on cell apoptosis in cancers remains rare. The present study aimed to explore the role of IL-37 in cell apoptosis in cervical cancer, and the involved apoptosis-related molecules. Methods: IL-37 was overexpressed by transfecting the pIRES2-EGFP-IL-37 plasmid in HeLa and C33A cells. Reverse transcription-quantitative polymerase chain reaction (RT-qPCR) was performed to detect the mRNA expression of IL-37, Bcl-2, Bax and Bim. Western blotting was performed to detect the protein expression of IL-37 and Bim. Cell apoptosis was detected by flow cytometry. Results: IL-37 upregulated the mRNA expression levels of Bim by 138.40% for HeLa (P<0.05) and 58.95% for C33A (P<0.05), and increased the protein expression levels of BimL by 69.10% (P<0.05) and 56.66% (P<0.05) in HeLa and C33A, respectively. Overexpression of IL-37 increased the apoptosis rates by 152.86% for HeLa (P<0.01) and 25.4% for C33A (P<0.05). Knockdown of Bim by specific siRNA interference fragments (SiBim) reduced the apoptosis rates by 36.00% for HeLa (P<0.05) and 14.66% for C33A (P<0.05). Compared with the IL-37 overexpression group, the apoptosis rate in cotransfecting the IL-37 overexpression plasmid and SiBim group decreased by approximately 31% (P<0.05) and 24.35% (P<0.05) in HeLa and C33A, respectively. Conclusion: IL-37 upregulated Bim in cervical cancer cells. Furthermore, IL-37 can promote cervical cancer cell apoptosis, but Bim knockdown decreased this promotion through IL-37. Thus, IL-37 can promote cervical cancer cell apoptosis, which involve the upregulation of Bim.

PFKFB3 promotes endotoxemia-induced myocardial dysfunction through inflammatory signaling and apoptotic induction.

Cardiac dysfunction is a vital complication during endotoxemia (ETM). Accumulating evidence suggests that enhanced glycolytic metabolism promotes inflammatory and myocardial diseases. In this study, we performed deep mRNA sequencing analysis on the hearts of control and lipopolysaccharide (LPS)-challenged mice (40 mg/kg, i.p.) and identified that the glycolytic enzyme, 6-phosphofructo-2-kinase (PFK-2)/fructose-2,6-bisphosphatase 3 (PFKFB3) might play an indispensable role in ETM-induced cardiac damage. Quantitative real-time PCR validated the transcriptional upregulation of PFKFB3 in the myocardium of LPS-challenged mice and immunoblotting and immunostaining assays confirmed that LPS stimulation markedly increased the expression of PFKFB3 at the protein level both in vivo and in vitro. The potent antagonist 3-(3pyridinyl)-1-(4-pyridinyl)-2-propen-1-one (3PO) was used to block PFKFB3 activity in vivo (50 mg/kg, i.p.) and in vitro (10 µM). Echocardiographic analysis and TUNEL staining showed that 3PO significantly alleviated LPS-induced cardiac dysfunction and apoptotic injury in vivo. 3PO also suppressed the LPS-induced secretion of tumor necrosis factor-α, interleukin (IL)-1ß, IL-6 and lactate in the serum, in addition to lactate in the myocardium. PFKFB3 inhibition also diminished the nuclear translocation and phosphorylation of transcription factor nuclear factor-κB (NF-κB) in both adult cardiomyocytes and HL-1 cells. Furthermore, immunoblotting analysis showed that 3PO inhibited LPS-induced apoptotic induction in cardiomyocytes. Taken together, these findings demonstrate that PFKFB3 participates in LPS-induced cardiac dysfunction via mediating inflammatory and apoptotic signaling pathway.

The Diagnostic Value of Chemokine/Chemokine Receptor Pairs in Hepatocellular Carcinoma and Colorectal Liver Metastasis.

Chemokines and their receptors have been proposed to play important roles in tumor progression and metastasis. To investigate their roles in the progression of primary and metastatic malignant liver tumors and their prognosis, we compared expression profiles of CXCL12/CXCR4, CCL20/CCR6, and CCL21/CCR7 in hepatocellular carcinoma (HCC) and colorectal liver metastases (CRLM). Immunohistochemistry was used to analyze the expression levels of the chemokine/chemokine receptor pairs in 29 HCC and 11 CRLM specimens and adjacent non-cancerous tissues, and correlations with clinicopathological variables and overall survival were determined. CCL20/CCR6 expression was higher in HCC than in adjacent non-cancerous tissues. High CCR6 expression in HCC was negatively associated with 5-year survival rate and was an independent prognostic factor for overall survival of HCC patients, whereas differences were not observed between CRLM and adjacent tissues. Furthermore, significantly higher expression of CCL21/CCR7 was found in CRLM than in HCC. In summary, the CCL20/CCR6 axis was elevated in HCC but not in CRLM, whereas the CCL21/CCR7 axis was elevated in CRLM but not in HCC.

Increased ZNF84 expression in cervical cancer.

PURPOSE: Little is known about ZNF84 gene. This study aims to investigate ZNF84 expression in cervical cancer (CC) and the effects of ZNF84 on CC. MATERIALS AND METHODS: Cervical cancer tissue specimens were collected from The First People's Hospital of Foshan. ZNF84 and Akt expression were detected by immunohistochemistry. The influence of ZNF84 on cell proliferation was detected by CCK-8 kits. The effects of ZNF84 on Akt protein and mRNA expression were detected by western blotting and qPCR, respectively. RESULTS: High expression of ZNF84 protein (80.0%) was detected within CC tissues while negative expression was found in normal cervical tissues. ZNF84 was specifically associated with tumor size (p = 0.018) and negatively associated with other indicators. Further, in squamous cell carcinoma, ZNF84 was associated with both TNM staging (p = 0.041) and tumor size (p = 0.041). In vitro, we used shZNF84 to inhibit the mRNA and protein expression of ZNF84, and showed marked inhibition of cancer cell proliferation by shZNF84. Furthermore, inhibition of ZNF84 down-regulated Akt. Ly294002 (an Akt inhibitor) decreased the cell inhibition ability of shZNF84, indicating the involvement of Akt. Finally, the relationship between ZNF84 and Akt in vivo showed positive correlation (p = 0.023). CONCLUSION: ZNF84 expression was increased in CC tissues and associated with tumor size. ZNF84 promoted cell proliferation which might involve Akt signal.

miR-135b reverses chemoresistance of non-small cell lung cancer cells by downregulation of FZD1.

BACKGROUND: Non-small cell lung cancer (NSCLC) chemoresistance usually limits the clinical efficacy of chemotherapeutic approaches. However, few reports have revealed the regulation of miR-135b and Frizzled-1 (FZD1) involved in NSCLC chemoresistance. METHODS: To identify the mechanism of miR-135b and FZD1 in NSCLC chemoresistance and to observe their biological functions, we detected the expression levels of miR-135b and FZD1 by conducting quantitative real-time polymerase chain reaction (RT-qPCR) and modified the expressions of miR-135b and FZD1 by transiently transfecting cells with miR-135b mimics or FZD1-siRNA. The 3'-untranslated region (3'-UTR) of FZD1 combined with miR-135b was verified through dual-luciferase reporter assay. RESULTS: Compared with that in A549 parental cell lines, the miR-135b expression in drug-resistant lung cancer cell lines (A549/DDP) was decreased and their FZD1 expression was increased. The increased miR-135b expression and silenced FZD1 expression enhanced the sensitivity of resistant cells to cisplatin treatment. The high expression of miR-135b in A549/DDP cells remarkably decreased the mRNA levels of FZD1. FZD1 was further identified as the functional downstream target of miR-135b by directly targeting the 3'-UTR of FZD1. CONCLUSION: The amplification of miR-135b suppressed NSCLC chemoresistance by directly mediating the FZD1 downregulation.

Efficacy of epidermal growth factor receptor inhibitors in combination with chemotherapy in advanced non-small cell lung cancer: a meta-analysis of randomized controlled trials.

The role of a combination of epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) and chemotherapy for non-small-cell lung cancer (NSCLC) has not been well established. To clarify this problem, we performed a meta-analysis with 15 studies identified from PubMed, EMBASE and the Cochrane Library. We found that the combined regimen had a significant benefit on progression-free survival (PFS) (hazard ratio (HR) = 0.80; 95% CI = 0.71-0.90; P < 0.001) and the objective response rate (ORR) (RR = 1.35; 95% CI = 1.14-1.59; P < 0.001). However, the combined regimen had no significant impact on overall survival (OS) (HR = 0.96; 95% CI = 0.90-1.03; P = 0.25). Subgroup analysis showed significantly higher OS advantages in EGFR mutation positive patients (P = 0.01), never smokers (P = 0.01), Asian patients (P = 0.02), patients receiving second-line treatment (P < 0.001), and those receiving a sequential combination of EGFR-TKIs and chemotherapy (P = 0.005). The combination regimen showed a higher incidence of grade 3-4 toxicities (leucopenia, neutropenia, febrile neutropenia, anemia, rash, fatigue and diarrhea). In summary, the combination of EGFR-TKIs plus chemotherapy in advanced NSCLC achieved a significantly longer PFS and a higher ORR but not longer OS. Well-designed prospective studies are needed to confirm these findings.

[TiO2-Induced Photodegradation of Levofloxacin by Visible Light and Its Mechanism].

Levofloxacin is an emerging pollutant. Single levofloxacin and TiO2 have no visible-light activity. However, photodegradation of levofloxacin dramatically enhanced in the presence of TiO2 under visible light irradiation. Considering this finding, he photodegradation of levofloxacin over TiO2 was investigated under visible light irradiation. Effects of TiO2 dosage, levofloxacin concentration, and solution pH on levofloxacin photodegradation were examined by monitoring its concentration decay with time. The results showed that levofloxacin photodegradation fitted the Langmuir-Hinshelwood kinetic model. Solution pH, TiO2 dose, and levofloxacin concentration had significant effects on the photodegradation rates. In addition, batch adsorption experiments revealed that adsorption of levofloxacin on TiO2 conformed to the pseudo-second-order kinetics and the Langmuir isotherm. DRS spectrum of levofloxacin-adsorbed TiO2 suggested that a surface complex was formed between levofloxacin and TiO2. Addition of radical scavengers and N2-degassing affecting levofloxacin photodegradation indicated that the superoxide ion radical was mainly active species. UV-Vis spectra of a deaerated TiO2 and levofloxacin suspensions further confirmed that the electron injection into TiO2 conduction band took place under visible light irradiation. Based on these results, a charge-transfer mechanism initiated by photoexcitation of TiO2/ levofloxacin surface complex was proposed for levofloxacin photocatalytic degradation over TiO2 under visible light. This study indicates that the charge-transfer-complex-mediated photocatalytic technique has promising applications in the removal of colorless organic pollutants.

Overexpressed ubiquitin ligase Cullin7 in breast cancer promotes cell proliferation and invasion via down-regulating p53.

Ubiquitin ligase Cullin7 has been identified as an oncogene in some malignant diseases such as choriocarcinoma and neuroblastoma. However, the role of Cullin7 in breast cancer carcinogenesis remains unclear. In this study, we compared Cullin7 protein levels in breast cancer tissues with normal breast tissues and identified significantly higher expression of Cullin7 protein in breast cancer specimens. By overexpressing Cullin7 in breast cancer cells HCC1937, we found that Cullin7 could promote cell growth and invasion in vitro. In contrast, the cell growth and invasion was inhibited by silencing Cullin7 in breast cancer cell BT474. Moreover, we demonstrated that Cullin7 promoted breast cancer cell proliferation and invasion via down-regulating p53 expression. Thus, our study provided evidence that Cullin7 functions as a novel oncogene in breast cancer and may be a potential therapeutic target for breast cancer management.

Reduction in ventricular tachyarrhythmias with statins in the Multicenter Automatic Defibrillator Implantation Trial (MADIT)-II.

OBJECTIVES: We evaluated whether statins have anti-arrhythmic effects by exploring the association of statin use with appropriate implantable cardioverter-defibrillator (ICD) therapy for ventricular tachycardia/ventricular fibrillation (VT/VF) in the Multicenter Automatic Defibrillator Implantation Trial (MADIT)-II. BACKGROUND: A few studies have suggested that lipid-lowering drugs may have anti-arrhythmic effects in patients with coronary artery disease. METHODS: Patients receiving an ICD (n = 654; U.S. centers only) in the MADIT-II study were categorized by the percentage of days each patient received statins during follow-up (90% to 100%, n = 386; 11% to 89%, n = 116; and 0% to 10%, n = 152). The Kaplan-Meier method with significance testing by the log-rank statistic and time-dependent proportional hazards regression analysis were used to evaluate the effect of statin use on the probability of ICD therapy for the combined end point VT/VF or cardiac death and for the end point VT/VF. RESULTS: The cumulative rate of ICD therapy for VT/VF or cardiac death, whichever occurred first, was significantly reduced in those with > or =90% statin usage compared to those with lower statin usage (p = 0.01). The time-dependent statin:no statin therapy hazard ratio was 0.65 (p < 0.01) for the end point of VT/VF or cardiac death and 0.72 (p = 0.046) for VT/VF after adjusting for relevant covariates. CONCLUSIONS: Statin use in patients with an ICD was associated with a reduction in the risk of cardiac death or VT/VF, whichever occurred first, and was associated with a reduction in VT/VF episodes. These findings suggest that statins have anti-arrhythmic properties.

Acute anticoagulation adjustment in patients with atrial fibrillation at risk for stroke: approaches, strategies, risks and benefits.

The acute management of anticoagulation in patients with atrial fibrillation to prevent stroke and other thromboembolic complications includes the use of individualized strategies tailored to the patient and based on the situation (cardioversion, surgeries, dental procedures, cardiac interventions, other invasive procedures and initiation of, or adjustment to, warfarin dosing). The vast range of choices can cause confusion and few randomized controlled clinical trials in this area provide adequate guidance. Chronic anticoagulation management is more straightforward since clinical evidence is ample, randomized clinical trial data provides cogent informaiton and guidelines have been established. Acute management of anticoagulation in patients with atrial fibrillation to prevent thromboembolic complications is often unrecognized but is emerging as a crucial, but challenging, and increasingly complex aspect of the care of patients with atrial fibrillation. This review addresses issues regarding such patients who may be at risk for stroke and require acute adjustments of anticoagulation (in light of, or in lieu of, chronic anticoagulation). Several promising new strategies are considered in light of established medical care. This analysis provides practical recommendations based on available data and presents results from recent investigations that may provide insight into future strategies.

Stereoselective synthesis of beta-amino acids.

A convenient method for the stereoselective syntheses of beta-amino acids with alpha-substitutions has been developed. This synthetic route involves the preparation of isoxazolidinones through hydroxylamine addition to unsaturated esters and subsequent hydrogenation. This procedure is also useful for the stereoselective syntheses of alpha-deuterated beta-amino acids.