In vitro study of the tocolytic effect of oroxylin A from Scutellaria baicalensis root

Scutellariae Radix is one of the well-known tocolytic Chinese herbs. Oroxylin A is isolated from the root of Scutellaria baicalensis. The main syndrome of preterm birth is caused by uterus contractions from excitatory factors. Administration of tocolytic agents is a strategy to prevent the occurrence of preterm births. The aim of this study was to investigate the effects of oroxylin A on contractions of uterine strips isolated from non-pregnant female Wistar rats (250~350 g). Contractions of the uterus were induced with acetylcholine (Ach) (1 μM), PGF2α (0.1 μM), oxytocin (10-3 U/ml), KCl (56.3 mM), tetraethylammonium (TEA; 1 and 10 mM), 4-aminopyridine (4-AP; 5 mM), glipizide (30 μM), a nitric oxide synthase (NOS) inhibitor (LNNA; 10-3M), a β-receptor blocker (propranolol; 10 μM), and a cyclooxygenase inhibitor (indomethacin; 60 μM). The inhibitory effects of the amplitude and frequency of spontaneous contractions by oroxylin A were antagonized with Ach (IC50 22.85 μM), PGF2α (IC5027.28 μM), oxytocin (IC50 12.34 μM), TEA; 1 and 10 mM (IC50 52.73 and 76.43 μM), 4-AP (IC50 67.16 μM), and glipizide (IC5027.53 μM), but oroxylin A was not influenced by Ca2+-free medium, LNNA, propranolol, or indomethacin. Otherwise, oroxylin A-mediated relaxation of the rat uterus might occur through opening of uterine calcium-dependent potassium channels or adenosine triphosphate potassium channel activation. This suggests that oroxylin A is the tocolytic principle constituent of Scutellariae Radix, and oroxylin A may provide a lead compound for new tocolytic drug development in the future

Comparison of the Prevalence of Metabolic Syndrome Between the Criteria for Taiwanese and Japanese and the Projected Probability of Stroke in Elderly Hypertensive Taiwanese

SummaryBackgroundThe cutoff of abdominal circumference for metabolic syndrome (MS) defined by the Bureau of Health Promotion (BHP) of Taiwan for Taiwanese (men, 90cm; women, 80cm) and by the International Diabetes Federation (IDF) for Japanese (men, 85cm; women, 90cm) differs. This study aimed to examine the impact of this difference on the prevalence of MS and the impact of an MS diagnosis on the projected risk of stroke in hypertensive Taiwanese.MethodsMS was examined in a sample of 3,472 hypertensive patients (aged 55–80 years; 1,709 women) across Taiwan. The 10-year probability of stroke estimated from the Framingham equation was compared between MS and non-MS patients.ResultsThe prevalence of MS using the BHP criteria was 59.2% using the BHP criteria (95% confidence interval, CI, 57.6–60.8%; men, 52.5%; women, 66.1%) and 48.9% by the IDF criteria (95% CI, 47.2–50.5%; men, 61.3%; women, 36.1%). Both criteria showed that, compared with non-MS, MS has higher predicted 10-year probability of stroke (BHP, 0.153 ± 0.115 vs. 0.133 ± 0.105; IDF, 0.159 ± 0.109 vs. 0.132 ± 0.112; both p < 0.001) because of the difference in women (BHP, 0.143 ± 0.124 vs. 0.102 ± 0.091; IDF, 0.147 ± 0.121 vs. 0.118 ± 0.110; both p < 0.001) rather than men (BHP, p = 0.21; IDF, p = 0.29).ConclusionBoth criteria demonstrate that MS is highly prevalent in elderly hypertensive patients in Taiwan. Additionally in women, but not men, the predicted probability of stroke is higher in MS than in non-MS patients. The diagnosis of MS is potentially useful for identifying elderly hypertensive females with an elevated risk of stroke in Taiwan

A Retrospective Cohort Study Comparing Stroke Recurrence Rate in Ischemic Stroke Patients With and Without Acupuncture Treatment.

Little was known about the effects of acupuncture on stroke recurrence. The aim of this study is to investigate whether ischemic stroke patients receiving acupuncture treatment have a decreased risk of stroke recurrence. A retrospective cohort study of 30,058 newly diagnosed cases of ischemic stroke in 2000 to 2004 was conducted based on the claims of Taiwan National Health Insurance Research Database. The use of acupuncture treatment and stroke recurrence were identified during the follow-up period from 2000 to 2009. This study compared the risk of stroke recurrence between ischemic stroke cohorts with and without acupuncture treatment by calculating adjusted hazard ratios (HRs) and 95% confidence intervals (CIs) of acupuncture associated with stroke recurrence in the Cox proportional hazard model. The stroke recurrence rate per 1000 person-years decreased from 71.4 without to 69.9 with acupuncture treatment (P &lt; 0.001). Acupuncture treatment was associated with reduced risk of stroke recurrence (HR 0.88; 95% CI 0.84-0.91). The acupuncture effect was noted in patients with or without medical treatment for stroke prevention but its impact decreased with aging of stroke patients. Compared with stroke patients without acupuncture treatment and medication therapy, the hazard ratios of stroke recurrence for those had medication therapy only, acupuncture only, and both were 0.42 (95% CI 0.38-0.46), 0.50 (95% CI 0.43-0.57), and 0.39 (95% CI 0.35-0.43), respectively. This study raises the possibility that acupuncture might be effective in lowering stroke recurrence rate even in those on medications for stroke prevention. Results suggest the need of prospective sham-controlled and randomized trials to establish the efficacy of acupuncture in preventing stroke

Computational modeling with forward and reverse engineering links signaling network and genomic regulatory responses: NF-κB signaling-induced gene expression responses in inflammation

<p>Abstract</p> <p>Background</p> <p>Signal transduction is the major mechanism through which cells transmit external stimuli to evoke intracellular biochemical responses. Diverse cellular stimuli create a wide variety of transcription factor activities through signal transduction pathways, resulting in different gene expression patterns. Understanding the relationship between external stimuli and the corresponding cellular responses, as well as the subsequent effects on downstream genes, is a major challenge in systems biology. Thus, a systematic approach is needed to integrate experimental data and theoretical hypotheses to identify the physiological consequences of environmental stimuli.</p> <p>Results</p> <p>We proposed a systematic approach that combines forward and reverse engineering to link the signal transduction cascade with the gene responses. To demonstrate the feasibility of our strategy, we focused on linking the NF-κB signaling pathway with the inflammatory gene regulatory responses because NF-κB has long been recognized to play a crucial role in inflammation. We first utilized forward engineering (Hybrid Functional Petri Nets) to construct the NF-κB signaling pathway and reverse engineering (Network Components Analysis) to build a gene regulatory network (GRN). Then, we demonstrated that the corresponding IKK profiles can be identified in the GRN and are consistent with the experimental validation of the IKK kinase assay. We found that the time-lapse gene expression of several cytokines and chemokines (TNF-α, IL-1, IL-6, CXCL1, CXCL2 and CCL3) is concordant with the NF-κB activity profile, and these genes have stronger influence strength within the GRN. Such regulatory effects have highlighted the crucial roles of NF-κB signaling in the acute inflammatory response and enhance our understanding of the systemic inflammatory response syndrome.</p> <p>Conclusion</p> <p>We successfully identified and distinguished the corresponding signaling profiles among three microarray datasets with different stimuli strengths. In our model, the crucial genes of the NF-κB regulatory network were also identified to reflect the biological consequences of inflammation. With the experimental validation, our strategy is thus an effective solution to decipher cross-talk effects when attempting to integrate new kinetic parameters from other signal transduction pathways. The strategy also provides new insight for systems biology modeling to link any signal transduction pathways with the responses of downstream genes of interest.</p

An Investigation of the Use of Traditional Chinese Medicine in Stroke Patients in Taiwan

Background. The use of complementary and alternative medicine in critical illness is increasing worldwide. This study investigates how traditional Chinese medicine (TCM) is used in stroke patients. Methods. Using Taiwan National Health Insurance reimbursement claims, we compared the annual use of TCM between stroke patients and general population, identifying 15,330 patients with a new onset of stroke in 2000–2009. The sociodemographic status and medical comorbidities between stroke patients receiving TCM services and those without using the service were compared. Results. The use of TCM was higher in stroke patients than in the general population, 27.9% versus 25.4% in 2000 and 32.7% versus 27.8% in 2009, respectively, and grew consistently from 2000 to 2009. Among stroke patients, women, younger patients, white-collar employees, higher-income residents, and those living in areas with more TCM physicians were more likely to use TCM. Stroke patients using rehabilitation services were more likely to have more TCM visits (OR = 2.28, 95% CI = 1.96–2.66) and higher expenditure on TCM (OR = 2.67, 95% CI = 2.29–3.12) compared with stroke patients without rehabilitation. Conclusion. TCM is popular and well accepted in Taiwan. Patients with stroke have a higher TCM utilization rate than people without stroke

Cytochrome P450 Metabolism of Betel Quid-Derived Compounds: Implications for the Development of Prevention Strategies for Oral and Pharyngeal Cancers

Betel quid (BQ) products, with or without tobacco, have been classified by the International Agency for Research on Cancer (IARC) as group I human carcinogens that are associated with an elevated risk of oral potentially malignant disorders (OPMDs) and cancers of the oral cavity and pharynx. There are estimated 600 million BQ users worldwide. In Taiwan alone there are 2 million habitual users (approximately 10% of the population). Oral and pharyngeal cancers result from interactions between genes and environmental factors (BQ exposure). Cytochrome p450 (CYP) families are implicated in the metabolic activation of BQ- and areca nut-specific nitrosamines. In this review, we summarize the current knowledge base regarding CYP genetic variants and related oral disorders. In clinical applications, we focus on cancers of the oral cavity and pharynx and OPMDs associated with CYP gene polymorphisms, including CYP1A1, CYP2A6, CYP2E1, and CYP26B1. Our discussion of CYP polymorphisms provides insight into the importance of screening tests in OPMDs patients for the prevention of oral and pharyngeal cancers. Future studies will establish a strong foundation for the development of chemoprevention strategies, polymorphism-based clinical diagnostic tools (e.g., specific single-nucleotide polymorphism (SNP) “barcodes”), and effective treatments for BQ-related oral disorders

Differential change in cortical and hippocampal monoamines, and behavioral patterns in streptozotocin-induced type 1 diabetes rats

Objective(s): Diabetes mellitus (DM) is a widespread metabolic disorder worldwide. Clinical physicians have found diabetic patients have mild to middle cognitive dysfunction and an alteration of brain monoaminergic function. This study explored the change in various patterns of behavioral models and brain monoamine function under streptozotocin (STZ)-induced type 1 diabetes.Materials and Methods: We established a type 1 DM model via intravenous injection with STZ (65 mg/kg) in rats. Three weeks after the STZ injection, various behavioral measurements including the inhibitory avoidance test, active avoidance test and Morris water maze were conducted. Finally, all rats were dissected and the concentrations of monoamines and their metabolites in cortex and hippocampus were measured by high performance liquid chromatography with electrochemical detection.Results: We found that STZ induced type 1 diabetes (hyperglycemia and lack of insulin) in rats. STZ-induced diabetic rats had cognitive impairment in acquisition sessions and long-term retention of the active avoidance test. STZ-induced diabetic rats also had cognitive impairment in spatial learning, reference and working memory of the Morris water maze. STZ significantly reduced concentrations of norepinephrine (NE) in the cortex and dopamine (DA) in the hippocampus, but increased concentrations of DA and serotonin (5-HT) in the cortex 35 days after injection. The concentration of 5-HT in the hippocampus was also significantly increased.Conclusion: The data suggested that this cognitive impairment after a short-term period of STZ injection might be related to cortical NE dysfunction, differential alteration of cortical and hippocampal DA function, and brain 5-HT hyperfunction