Antiplatelet and antithrombotic effects of cordycepin-enriched WIB-801CE from Cordyceps militaris ex vivo, in vivo, and in vitro.

BACKGROUND: A species of the fungal genus Cordyceps has been used as a complementary and alternative medicine of traditional Chinese medicine, and its major component cordycepin and cordycepin-enriched WIB-801CE are known to have antiplatelet effects in vitro. However, it is unknown whether they have also endogenous antiplatelet and antithrombotic effects. In this study, to resolve these doubts, we prepared cordycepin-enriched WIB-801CE, an ethanol extract from Cordyceps militaris-hypha, then evaluated its ex vivo, in vivo, and in vitro antiplatelet and antithrombotic effects. METHODS: Ex vivo effects of WIB-801CE on collagen- and ADP-induced platelet aggregation, serotonin release, thromboxane A2 (TXA2) production and its associated activities of enzymes [cyclooxygenase-1 (COX-1), TXA2 synthase (TXAS)], arachidonic acid (AA) release and its associated phosphorylation of phospholipase Cß3, phospholipase Cγ2 or cytosolic phospholipase A2, mitogen-activated protein kinase (MAPK) [p38 MAPK, extracellular signal-regulated kinase (ERK)], and blood coagulation time in rats were investigated. In vivo effects of WIB-801CE on collagen plus epinephrine-induced acute pulmonary thromboembolism, and tail bleeding time in mice were also inquired. In vitro effects of WIB-801CE on cytotoxicity, and fibrin clot retraction in human platelets, and nitric oxide (NO) production in RAW264.7 cells or free radical scavenging activity were studied. RESULTS: Cordycepin-enriched WIB-801CE inhibited ex vivo platelet aggregation, TXA2 production, AA release, TXAS activity, serotonin release, and p38 MAPK and ERK2 phosphorylation in collagen- and ADP-activated rat platelets without affecting blood coagulation. Furthermore, WIB-801CE manifested in vivo inhibitory effect on collagen plus epinephrine-induced pulmonary thromboembolism mice model. WIB-801CE inhibited in vitro NO production and fibrin clot retraction, but elevated free radical scavenging activity without affecting cytotoxicity against human platelets. CONCLUSION: WIB-801CE inhibited collagen- and ADP-induced platelet activation and its associated thrombus formation ex vivo and in vivo. These were resulted from down-regulation of TXA2 production and its related AA release and TXAS activity, and p38MAPK and ERK2 activation. These results suggest that WIB-801CE has therapeutic potential to treat platelet activation-mediated thrombotic diseases in vivo.

Relationships Among Health Literacy, Self-Efficacy, Self-Management, and HbA1c Levels in Older Adults with Diabetes in South Korea: A Cross-Sectional Study.

Purpose: This study investigated the levels of health literacy, self-efficacy, self-management, and glycated hemoglobin (HbA1c) levels in older adults with diabetes to identify the relationships between these factors. Patients and Methods: This descriptive study consisted of 162 elderly outpatients with diabetes at the departments of endocrinology of three general hospitals in J Province, South Korea. Data were collected using a structured self-report questionnaire between October 21 and November 16, 2019. The data were analyzed using SPSS/WIN version 23.0. Results: Health literacy was positively correlated with self-efficacy (rs=0.64, p<0.001) and self-management (rs=0.44, p<0.001) and significantly negatively correlated with HbA1c levels (rs=-.42, p<0.001). Self-efficacy showed a significantly positive correlation with self-management (rs=0.65, p<0.001) and a significantly negative correlation with HbA1c levels (rs=-.30, p<0.001). Moreover, a significant negative correlation was found between self-management and HbA1c levels (rs=-.35, p<0.001). Hence, health literacy and patient self-management levels were associated with HbA1c levels in older adults with DM. Conclusion: Health education for community-dwelling older adults with diabetes should consider their health literacy levels. Moreover, measures to improve self-management abilities may be needed when developing educational programs for older adults with diabetes.

Putative TetR family transcriptional regulator SCO1712 encodes an antibiotic downregulator in Streptomyces coelicolor.

A tetR family transcriptional regulatory gene (SCO1712) was identified as a global antibiotic regulatory gene from a Streptomyces interspecies DNA microarray analysis. SCO1712 disruption in Streptomyces coelicolor not only upregulated antibiotic biosynthesis through pathway-specific regulators when a previously identified pleiotropic downregulatory wblA was expressed but also further stimulated antibiotic production in a wblA deletion mutant, implying that SCO1712 might encode a novel antibiotic downregulator.

Isolation and genetic manipulation of the antibiotic down-regulatory gene, wblA ortholog for doxorubicin-producing Streptomyces strain improvement.

Cross-genome comparative transcriptome analyses were previously conducted using the sequenced Streptomyces coelicolor genome microarrays to understand the genetic nature of doxorubicin (DXR) and daunorubicin (DNR) overproducing industrial mutant (OIM) of Streptomyces peucetius. In this previous work, a whiB-like putative transcription factor (wblA ( sco )) was identified as a global antibiotic down-regulator in S. coelicolor (Kang et al., J Bacteriol 189:4315-4319, 2007). In this study, a total genomic DNA library of a DXR/DNR-overproducing S. peucetius OIM was constructed and screened using wblA ( sco ) as a probe, resulting in the isolation of a wblA ortholog (wblA ( spe )) that had 95% amino acid identity to wblA ( sco ). Gene disruption of wblA ( spe ) from the S. peucetius OIM resulted in an approximately 70% increase in DXR/DNR productivity, implying that the DXR/DNR production in the S. peucetius OIM could be further improved via comparative transcriptomics-guided target gene manipulation. Furthermore, several putative wblA ( spe ) -dependent genes were also identified using S. coelicolor interspecies DNA microarray analysis between the S. peucetius OIM and wblA ( spe )-disrupted S. peucetius OIM. Among the genes whose expressions were significantly stimulated in the absence of wblA ( spe ), the overexpression of a conserved hypothetical protein (SCO4967) further stimulated the total production of DXR/DNR/akavinone by 1.3-fold in the wblA ( spe )-disrupted S. peucetius OIM, implying that the sequential genetic manipulation of target genes identified from interspecies comparative microarray analysis could provide an efficient and rational strategy for Streptomyces strain improvement.