Heptaellipside A, a rare new 2,28-bidesmosidic lupane-type saponin from the leaves of .

For the first time, phytochemical constituents of the leaves of were investigated. One rare new 2,28-bidesmosidic lupane-type saponin, named heptaellipside A (), along with four other lupane-type analogs () were purified by combining differently chromatographic methods. All of the separated compounds () were communicated for the first time from .

Adult granulosa cell tumour of the ovary incidentally discovered during caesarean section in a pregnant patient after IVF: a rare case and a review of the literature.

Adult granulosa cell tumours (AGCTs) of the ovary are very rare during pregnancy. To date, only five cases of ovarian AGCT in pregnancy have been reported in the literature and the patients all conceived spontaneously. We report a case of AGCT of the ovary that was incidentally discovered during a caesarean section in a patient undergoing In vitro fertilisation (IVF).

A statistical approach to boost soluble expression of E. coli-derived virus-like particles in shake-flask cultivation.

Hepatitis B core virus-like particles (HBc-VLP) have been widely used as carrier platforms to present an epitope of interest. Escherichia coli expression system is cost effective and produces high yields of recombinant protein. However major drawbacks include difficulties in obtaining soluble expression and tendency to form inclusion bodies.

Severe COVID-19 during pregnancy treated with pulse corticosteroid therapy and mid-trimester termination: A case report.

Background: At the early stage of the pandemic, severe COVID-19 was thought to be rare among pregnant women. However, cumulating data showed that gestational state is a risk factor for severe pneumonia, particularly due to the hyperinflammatory state. Recent reports suggested the efficacy of pulse corticosteroids in stopping the cytokine storm in people infected with SARS-CoV-2, but limited data exists regarding its use in pregnant women.

Murine Drinking Models in the Development of Pharmacotherapies for Alcoholism: Drinking in the Dark and Two-bottle Choice.

Alcohol Use Disorder (AUD) is a major problem with more than an estimated 76 million people worldwide meeting the diagnostic criteria. Current treatments are limited to three FDA-approved medications that are largely ineffective even when combined with psychosocial intervention, as is evident by the high relapse rate. As such, the search for more novel treatments represents an important public health goal.

Preclinical evaluation of avermectins as novel therapeutic agents for alcohol use disorders.

The deleterious effects of alcohol use disorders (AUDs) on human health have been documented worldwide. The enormous socioeconomic burden coupled with lack of efficacious pharmacotherapies underlies the need for improved treatment strategies. At present, there is a growing body of preclinical evidence that demonstrates the potential of avermectins [ivermectin (IVM), selamectin (SEL), abamectin (ABM), and moxidectin (MOX)] in treatment of AUDs.

Reduced expression of purinergic P2X4 receptors increases voluntary ethanol intake in C57BL/6J mice.

Purinergic P2X4 receptors (P2X4Rs) belong to the P2X superfamily of ionotropic receptors that are gated by adenosine 5'-triphosphate (ATP). Accumulating evidence indicates that P2X4Rs play an important role in regulation of ethanol intake. At the molecular level, ethanol's inhibitory effects on P2X4Rs are antagonized by ivermectin (IVM), in part, via action on P2X4Rs.

Preclinical development of moxidectin as a novel therapeutic for alcohol use disorder.

Current pharmacotherapies for alcohol used disorder (AUD) are few and relatively ineffective illustrating the need for the development of new, effective medications. Using a translational approach, our laboratory reported that ivermectin, an FDA-approved, human and animal anti-parasitic agent, can significantly reduce ethanol intake in male and female mice across different drinking paradigms. Extending this line of investigation, the current paper investigated the utility of moxidectin (MOX), an analogue of ivermectin, to reduce ethanol intake.

Utilizing an Orally Dissolving Strip for Pharmacological and Toxicological Studies: A Simple and Humane Alternative to Oral Gavage for Animals.

Prior to testing novel therapeutics in humans, short and long term preclinical (i.e., animal), repetitive pharmacological and toxicological testing is required.

Oral delivery of ivermectin using a fast dissolving oral film: Implications for repurposing ivermectin as a pharmacotherapy for alcohol use disorder.

Individuals suffering from an alcohol-use disorder (AUD) constitute a major health concern. Preclinical studies in our laboratory show that acute and chronic intraperitoneal (i.p.

Multiday administration of ivermectin is effective in reducing alcohol intake in mice at doses shown to be safe in humans.

Ivermectin (IVM), an FDA approved anthelmintic agent, can significantly reduce ethanol intake in mice following acute administration. The current study evaluates the sustainability and safety of multiday IVM administration in reducing 10% v/v ethyl alcohol (10E) intake in mice at a dose shown to be safe in humans. We tested the effect of 10-day administration of IVM (3.

Ivermectin reduces alcohol intake and preference in mice.

The high rate of therapeutic failure in the management of alcohol use disorders (AUDs) underscores the urgent need for novel and effective strategies that can deter ethanol consumption. Recent findings from our group showed that ivermectin (IVM), a broad-spectrum anthelmintic with high tolerability and optimal safety profile in humans and animals, antagonized ethanol-mediated inhibition of P2X4 receptors (P2X4Rs) expressed in Xenopus oocytes. This finding prompted us to hypothesize that IVM may reduce alcohol consumption; thus, in the present study we investigated the effects of this agent on several models of alcohol self-administration in male and female C57BL/6 mice.

The SRSF1 linker induces semi-conservative ESE binding by cooperating with the RRMs.

SR proteins promote spliceosome formation by recognizing exonic splicing enhancers (ESEs) during pre-mRNA splicing. Each SR protein binds diverse ESEs using strategies that are yet to be elucidated. Here, we show that the RNA-binding domain (RBD) of SRSF1 optimally binds to decameric purine rich ESE sequences although locations of purines are not stringently specified.

Allosteric interactions direct binding and phosphorylation of ASF/SF2 by SRPK1.

ASF/SF2, a member of the serine-arginine (SR) protein family, has two RRM domains (RRM1 and RRM2) and a C-terminal domain rich in RS dipeptides. SR protein kinase 1 (SRPK1) phosphorylates approximately 12 of these serines using a semiprocessive mechanism. The X-ray structure of the ASF/SF2-SRPK1 complex revealed several features of the complex that raised intriguing questions about how the substrate is phosphorylated by the kinase.

A sliding docking interaction is essential for sequential and processive phosphorylation of an SR protein by SRPK1.

The 2.9 A crystal structure of the core SRPK1:ASF/SF2 complex reveals that the N-terminal half of the basic RS domain of ASF/SF2, which is destined to be phosphorylated, is bound to an acidic docking groove of SRPK1 distal to the active site. Phosphorylation of ASF/SF2 at a single site in the C-terminal end of the RS domain generates a primed phosphoserine that binds to a basic site in the kinase.

Structurally unique yeast and mammalian serine-arginine protein kinases catalyze evolutionarily conserved phosphorylation reactions.

The mammalian serine-arginine (SR) protein, ASF/SF2, contains multiple contiguous RS dipeptides at the C terminus, and approximately 12 of these serines are processively phosphorylated by the SR protein kinase 1 (SRPK1). We have recently shown that a docking motif in ASF/SF2 specifically interacts with a groove in SRPK1, and this interaction is necessary for processive phosphorylation. We previously showed that SRPK1 and its yeast ortholog Sky1p maintain their active conformations using diverse structural strategies.