Wuzi Yanzong Decoction Ameliorates Oligoasthenozoospermia by Up-Regulating Methyltransferase and Increasing Spata, Bcl, and Pik3 Series Genes Methylation Level.

Wuzi Yanzong decoction (WZYZD) belongs to the traditional formula for treating male infertility caused by oligoasthenozoospermia (OLI). This research aims to elucidate the therapeutic substance basis and potential pharmacological mechanisms of WZYZD in treating OLI. A total of 52 chemical ingredients were identified from WZYZD.

Betaine alleviates spermatogenic cells apoptosis of oligoasthenozoospermia rat model by up-regulating methyltransferases and affecting DNA methylation.

Background: Oligoasthenozoospermia is the most common type of semen abnormality in male infertile patients. Betaine (BET) has been proved to have pharmacological effects on improving semen quality. BET also belongs to endogenous physiological active substances in the testis.

Dopey2 and Pcdh7 orchestrate the development of embryonic neural stem cells/ progenitors in zebrafish.

DOPEY2 has been shown to be associated with Down syndrome and PCDH7 might be involved in Rett syndrome and duplication syndrome. The mechanism how both proteins play roles in these syndromes are largely unknown. Here, we show that Dopey2 and Pcdh7 balance the proliferation and differentiation of neural stem cells and progenitors during embryonic neurogenesis to generate proper size and architecture of zebrafish brains.

Solitary fibrous tumor of the central nervous system invading and penetrating the skull: A case report.

Solitary fibrous tumor (SFT) of the central nervous system is a rare spindle cell tumor of mesenchymal origin. The present study reports the case of a 44-year-old male patient with SFT. Magnetic resonance imaging demonstrated that the majority of the intracranial tumors exhibited uneven low signals on T1-weighted imaging (T1WI) and low mixed signals on T2WI, and there was an enhancement on enhanced scanning.

Discovery of 1'-(1-phenylcyclopropane-carbonyl)-3H-spiro[isobenzofuran-1,3'-pyrrolidin]-3-one as a novel steroid mimetic scaffold for the potent and tissue-specific inhibition of 11β-HSD1 using a scaffold-hopping approach.

11β-hydroxysteroid dehydrogenase 1 (11β-HSD1) has been identified as the primary enzyme responsible for the activation of hepatic cortisone to cortisol in specific peripheral tissues resulting in the concomitant antagonism of insulin action within these tissues. Dysregulation of 11β-HSD1, particularly in adipose tissues, has been associated with metabolic syndrome and type 2 diabetes mellitus. Therefore, inhibition of 11β-HSD1 with a small nonsteroidal molecule is therapeutically desirable.

Metabolic profiling and pharmacokinetic studies of sinapine thiocyanate by UHPLC-Q/TOF-MS and UHPLC-MS/MS.

Sinapine thiocyanate (ST) is an index component and pharmacological active component of Semen Sinapis and Semen Raphani, and it is widely used to relieving cough and asthma. This study aimed to obtain the metabolic and pharmacokinetic characterization of ST. The metabolic profiles of ST were obtained from rat plasma, urine, and feces via ultra-performance liquid chromatography-quadrupole-time-of-flight mass spectrometry (UHPLC-Q/TOF-MS).

Biotransformation patterns of dictamnine in vitro/in vivo and its relative molecular mechanism of dictamnine-induced acute liver injury in mice.

Dictamnine (DIC), a typical furan-quinoline alkaloid, has a wide range of pharmacological and toxicological effects, such as anti-bacterial, antifungal, anti-cancer, and hepatoxicity. But the molecular mechanism of DIC-induced hepatoxicity in mice remains unclear. This study aimed to clarify the biotransformation patterns of DIC in vitro/in vivo and the relative molecular mechanism of DIC-induced hepatoxicity in mice.

Pharmacokinetic studies of ginsenosides Rk1 and Rg5 in rats by UFLC-MS/MS.

A rapid ultra-fast liquid chromatography tandem mass spectrometry method was developed and validated to determine ginsenosides Rk1 and Rg5, a pair of isomers, in rat plasma, which was successfully applied to their pharmacokinetic studies. Two ginsenosides were given to male Sprague-Dawley rats via intragastrical and intravenous routes, respectively, and the impact of double bond position on the pharmacokinetic features of the two ginsenosides was elucidated in rats. Ginsenoside Rg3 was used as internal standard and ethyl acetate was applied to extract analytes and internal standard.

Dynamic changes in chemical compositions and anti-acetylcholinesterase activity associated with steaming process of stem-leaf saponins of Panax notoginseng.

Stem-leaf saponins (SLSs), the total saponins from aerial part of P. notoginseng, are by-products of notoginseng, a famous traditional Chinese medicine. SLSs have been used as a health functional food in China, but its mild effects limited clinical applications in diseases.

Metabolites identification and reversible interconversion of chelerythrine and dihydrochelerythrine in vitro/in vivo in rats using ultra-performance liquid chromatography combined with electrospray ionization quadrupole time-of-flight tandem mass spectrometry.

Chelerythrine (CHE) and dihydrochelerythrine (DHCHE), two typical benzophenanthridine alkaloids, have a wide range of pharmacological activities, such as antibacterial, anti-tumour and antiparasitic activities. To date, the biological activities of CHE and DHCHE are well reported, but the biotransformation of CHE and DHCHE in vivo remains unknown. This study aims to clarify the metabolic pathway of CHE and DHCHE in rat liver microsomes (RLMs) in vitro and in vivo.

[Treatment efficacy of Solitaire stent- and LVIS stent-assisted coil embolization for intracranial wide-neck carotid aneurysm].

Objective: To compare the safety, efficacy and complications of LVIS stent-assisted coil embolization and Solitaire stent-assisted coil embolization for management of intracranial wide-neck carotid aneurysms.

Methods: We retrospectively analyzed the data of 86 patients with intracranial wide-neck carotid aneurysm treated in our hospital between June, 2016 and June, 2019. Forty-three of the patients received LVIS stent-assisted coil tamponade and the other 43 received Solitaire stentassisted coil tamponade.

Rapid identification and pharmacokinetic studies of multiple active alkaloids in rat plasma through UPLC-Q-TOF-MS and UPLC-MS/MS after the oral administration of Zanthoxylum nitidum extract.

Zanthoxylum nitidum (Roxb.) DC. (ZN) belongs to the genus Zanthoxylum of Rutaceae and has various chemical ingredients and pharmacologic effects.

Identification and characterization of forced degradation products and stability-indicating assay for notoginsenosidefc by using UHPLC-Q-TOF-MS and UHPLC-MS/MS: Insights into stability profile and degradation pathways.

Notoginsenoside Fc, a protopanaxadiol-type saponin, shows multi-pharmacological activities. Chemical stability evaluation plays a crucial role in drug development. In this study, the forced degradation behavior of Notoginsenoside Fc was investigated under hydrolytic and oxidative conditions.

Analogous β-Carboline Alkaloids Harmaline and Harmine Ameliorate Scopolamine-Induced Cognition Dysfunction by Attenuating Acetylcholinesterase Activity, Oxidative Stress, and Inflammation in Mice.

The analogous β-carboline alkaloids, harmaline (HAL) and harmine (HAR), possess a variety of biological properties, including acetylcholinesterase (AChE) inhibitory activity, antioxidant, anti-inflammatory, and many others, and have great potential for treating Alzheimer's disease (AD). However, studies have showed that the two compounds have similar structures and AChE inhibitory activities but with significant difference in bioavailability. The objective of this study was to comparatively investigate the effects of HAL and HAR in memory deficits of scopolamine-induced mice.

Spongipyran Synthetic Studies. Total Synthesis of (+)-Spongistatin 2.

Evolution of a convergent synthetic strategy to access (+)-spongistatin 2 (2), a potent cytotoxic marine macrolide, is described. Highlights of the synthesis include: development of a multicomponent dithiane-mediated linchpin union tactic, devised and implemented specifically for construction of the spongistatin AB and CD spiro ring systems; application of a Ca(II) ion controlled acid promoted equilibration to set the thermodynamically less stable axial-equitorial stereogenicity in the CD spiroketal; use of sulfone addition/Julia methylenation sequences to unite the AB and CD fragments and introduce the C(44)-C(51) side chain; and fragment union and final elaboration to (+)-spongistatin 2 (2) exploiting Wittig olefination to unite the advanced ABCD and EF fragments, followed by regioselective Yamaguchi macrolactonization and global deprotection. Correction of the CD spiro ring stereogenicity was subsequently achieved via acid equilibration in the presence of Ca(II) ion to furnish (+)-spongistatin 2 (2).

Enantioselective synthesis of Janus kinase inhibitor INCB018424 via an organocatalytic aza-Michael reaction.

An enantioselective synthesis of INCB018424 via organocatalytic asymmetric aza-Michael addition of pyrazoles (16 or 20) to (E)-3-cyclopentylacrylaldehyde (23) using diarylprolinol silyl ether as the catalyst was developed. Michael adducts (R)-24 and (R)-27 were isolated in good yield and high ee and were readily converted to INCB018424.

Discovery of a potent, selective, and orally active human epidermal growth factor receptor-2 sheddase inhibitor for the treatment of cancer.

The design, synthesis, evaluation, and identification of a novel class of (6S,7S)-N-hydroxy-6-carboxamide-5-azaspiro[2.5]octane-7-carboxamides as the first potent and selective inhibitors of human epidermal growth factor receptor-2 (HER-2) sheddase is described. Several compounds were identified that possess excellent pharmacodynamic and pharmacokinetic properties and were shown to decrease tumor size, cleaved HER-2 extracellular domain plasma levels, and potentiate the effects of the humanized anti-HER-2 monoclonal antibody (trastuzumab) in vivo in a HER-2 overexpressing cancer murine xenograft model.

Identification of ADAM10 as a major source of HER2 ectodomain sheddase activity in HER2 overexpressing breast cancer cells.

Overexpression and activating mutations of ErbB family members have been implicated in the development and progression of a variety of tumor types. Cleavage of the HER2 receptor by an as yet unidentified ectodomain sheddase has been shown to liberate the HER2 extracellular domain (ECD) leaving a fragment with constitutive kinase activity that can provide ligand-independent growth and survival signals to the cell. This process is clinically relevant since HER2 ECD serum levels in metastatic breast cancer patients are associated with a poorer prognosis.