Discovery of Ethyl Ketone-Based Highly Selective HDACs 1, 2, 3 Inhibitors for HIV Latency Reactivation with Minimum Cellular Potency Serum Shift and Reduced hERG Activity.

We describe the discovery of histone deacetylase (HDACs) 1, 2, and 3 inhibitors with ethyl ketone as the zinc-binding group. These HDACs 1, 2, and 3 inhibitors have good enzymatic and cellular activity. Their serum shift in cellular potency has been minimized, and selectivity against hERG has been improved. They are also highly selective over HDACs 6 and 8. These inhibitors contain a variety of substituted heterocycles on the imidazole or oxazole scaffold. Compounds 31 and 48 stand out due to their good potency, high selectivity over HDACs 6 and 8, reduced hERG activity, optimized serum shift in cellular potency, and good rat and dog PK profiles.

Acupuncture and moxibustion therapy for scapulohumeral periarthritis: Protocol for an overview of systematic reviews and meta-analysis.

BACKGROUND: Scapulohumeral periarthritis (SP) is a very common painful shoulder disorder. Several systematic reviews (SRs) and meta-analyses have reported the effectiveness of acupuncture for patients with SP. However, the evidence has not been systematically synthesized. This overview aims to map, synthesize, and assess the reliability of evidence generated from these SRs and meta-analyses of acupuncture for SP. METHODS: We will electronically search the following databases for literature, regardless of publication status and language: the Cochrane Central Register of Controlled Trials (CENTRAL); PubMed; EMBASE; China National Knowledge Infrastructure (CNKI); Chinese Biomedical Literature Database (CBM); Chinese Scientific Journal Database (VIPdatabase); and Wan-Fang Database. In order to ensure the comprehensiveness and accuracy of the literature retrieval, we will combine the Suggestions of evidence-based medicine experts with the actual situation in the literature retrieval process to formulate the retrieval strategy, and make corresponding records to find the most appropriate retrieval strategy. The reference lists and the citation lists of studies meeting the inclusion criteria and relevant SRs will also be searched to identify further studies for inclusion. Before this review completed, the two reviewers will conduct the searching once again to ensure the latest studies could be included. ETHICS AND DISSEMINATION: Ethical approval is not required for overviews. We plan to publish results in peer-reviewed journals and present at international and national academic, clinical, and patient conferences. RESULTS: The results will be published in a peer-reviewed journal. CONCLUSION: This overview will provide comprehensive evidence of acupuncture for patients with SP. INPLASY REGISTRATION NUMBER: INPLASY202060020.

[Studies on chemical components of essential oil of crude semen sinapis and roasted semen sinapis].

OBJECTIVE: To study the chemical components of the essential oil of the Semen Sinapis with the different processing methods. METHOD: The essential oils of the crude Semen Sinapis and the roasted Semen Sinapis were extracted by steam distillation. The chemical components were analyzed by means of GC-MS-DS. The relative content of each component was calculated by area normalization. RESULT: The main chemical components of the essential oil of the crude Semen Sinapis and the roasted Semen Sinapis were similar. The main chemical components were allyl isothiocyanate and 4-isothio-cyanato-1-butene. The chemical components of the essential oil of the crude Semen Sinapis were more than that of the roasted Semen Sinapis. CONCLUSION: The effect of different processing methods on the chemical components of the essential oil of Semen Sinapis was significant. Certain chemical components such as isothiocyanato-containing substances, were found in the crude Semen Sinapis.

Demonstration of enhanced endogenous fibrinolysis in thrombin activatable fibrinolysis inhibitor-deficient mice.

To investigate the importance of thrombin activatable fibrinolysis inhibitor (TAFI) in the stabilization of plasma clots, we have compared fibrinolysis in TAFI-deficient (KO) and wild-type (WT) littermate mice. TAFI-deficient mice were previously generated by targeted gene disruption. The level of TAFI activity generated in plasma from WT mice in the presence of added thrombin and thrombomodulin (activatable TAFI) is twice that of plasma from TAFI heterozygous mice (HET); no activatable TAFI is detected in TAFI KO plasma. In vitro, TAFI KO plasma clots lysed faster than WT plasma clots, and HET plasma clots lysed at an intermediate rate. The rate of clot lysis for KO mice is not changed in the presence of potato carboxypeptidase inhibitor, a specific inhibitor of TAFIa, whereas the WT and HET clot lysis rates are increased in the presence of potato carboxypeptidase inhibitor. C-terminal lysine residues are preserved on partially degraded clots from KO mice, but are absent from partially degraded WT clots. In vivo, in a batroxobin-induced pulmonary embolism model, KO mice displayed a lower retention of fibrin in the lungs than did WT mice. These results are the first demonstration of enhanced endogenous fibrinolysis in an in vivo model without the addition of exogenous thrombolytic.

[An experimental study(II) on the inhibition of prostatic hyperplasia by extract of seeds of Brassica alba].

OBJECTIVE: To study the active components and their functionary mechanism of the extract of Brassica alba seeds, which inhibits experimental mice prostatic hyperplasia. METHOD: Prostatic hyperplasia of castrated male mice induced by testosterone propionate, the penetrability of capillary vessel of mice skin induced by histamine and the endermic flesh bud of rat induced by filter paper were used as experimental models. Sinalbin and beta-sitosterol separated from seeds of Brassica alba were used to test the activities. RESULT: Sinalbin and beta-sitosterol(16.0 mg.kg-1.d-1 and 8.0 mg.kg-1.d-1) could significantly inhibit mice prostatic hyperplasia induced by testosterone propionate and activity of serum acid phosphatase(P < 0.01 or P < 0.05), Sinalbin(16.0 mg.kg-1.d-1)could significantly inhibit the hyperplasia of endermic flesh bud in rat induced by filter paper(P < 0.05), beta-sitosterol(16.0 mg.kg-1.d-1 and 8.0 mg.kg-1.d-1) could significantly decrease the penetrability of capillary vessel of mice skin induced by histamine. CONCLUSION: Sinalbin and beta-sitosterol have anti-androgen and anti-inflammation activities.

[An experimental study(I) on the inhibition of prostatic hyperplasia with extract of seeds of Brassica alba].

OBJECTIVE: To study the effective fraction of the extract of seeds of Brassica alba, which inhibits experimental mice prostatic hyperplasia. METHOD: An experimental model of prostatic hyperplasia of castrated male mice induced by testosterone propionate was made. Fractions I, II and III were prepared by extracting the seeds of Brassica alba successively with ether, ethanol and water under reflux. Total extract was prepared by extracting the seeds of Brassica alba with 60% ethanol under reflux. The total extract and the three fractions were used to test the activities. RESULT: Total extract, fractions I and II could not only significantly inhibit mice prostatic hyperplasia induced by testosterone propionate and activity of serum acid phosphatase, but also decrease wet weight of preputial glands, while fraction III is inactive. CONCLUSION: Extract from seeds of Brassica alba can significantly inhibit mice prostatic hyperplasia induced by exterior hormone, possessing an activity of anti-androgen. Fractions I and II show an equivalent activity of total extract, which indicate that these fractions contain active components of seeds of Brassica alba which can inhibit prostatic hyperplasia.