Progesterone resistance is mediated through epigenetic modification through SirT1 activation and is thought to contribute to infertility and progression of endometriosis. Endometriosis is a leading cause of unexplained IVF failure secondary to inflammatory changes that induce SirT1. The current study is designed to investigate a small molecule inhibitor of SirT1, in the clinical setting of In Vitro Fertilization and Embryo Transfer. The SAFER trial will compare EX-527 to placebo in a randomized, double-blind trial. Primary endpoints include Live Birth Rate (LBR) and secondary outcomes include pregnancy rate (PR), miscarriage rate (MR) and implantation failure rate.

开始日期2022-01-01

申办/合作机构

Wake Forest School of Medicine

NCT01521585

/ Completed临床2期

A Double-blind, Placebo-controlled Study in Huntington's Disease Patients to Determine the Safety and Tolerability of SEN0014196

The principal aim of this study is to obtain safety and tolerability data when SEN0014196 is administered orally over 12 weeks to male and female patients with Huntington's Disease.

开始日期2011-11-01

申办/合作机构

Siena Biotech SpA

NCT01485965

/ Completed临床1期

A Phase 1b, Open-label, Parallel-group Study in Subjects With Huntington Disease to Assess the Safety, Tolerability, and Fed/Fasted Pharmacokinetics of Repeated Oral Doses of SEN0014196

The primary purpose of this study is to assess the effect of food upon the pharmacokinetics (PK) of SEN0014196 in subjects with Huntington disease (HD).

开始日期2011-11-01

申办/合作机构

Siena Biotech SpA

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100 项与 Selisistat 相关的转化医学

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100 项与 Selisistat 相关的专利（医药）

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1,085

项与 Selisistat 相关的文献（医药）

2026-01-01·MICROBIAL PATHOGENESIS

Resveratrol inhibits porcine deltacoronavirus infection by activating SIRT1 to promote interferon production in vitro

Article

作者: Zhang, Chunhong ; Wang, Songqi ; Su, Renwei ; Shen, Haiyan ; Hou, Liting ; Nie, Jingjing ; Liu, Zhicheng ; Zhang, Jianfeng ; Lu, Yu ; Qu, Yunzhi ; Chen, Jin

Porcine deltacoronavirus (PDCoV) is a major pathogen that causes clinical diarrhea in piglets, resulting in substantial economic losses to the pig farming industry. Because of its host diversity, PDCoV can infect multiple species such as cattle, chickens, turkeys, mice, and even humans, posing a considerable threat to public health security. Currently, effective commercial drugs for PDCoV infection remain unavailable. In this study, we noted that resveratrol (Res) treatment effectively inhibited PDCoV replication in the porcine small intestinal epithelial cell line, IPEC-J2. Mechanistically, Res treatment increased SIRT1 expression, and the SIRT1 inhibitor EX-527 could block Res's antiviral activity. SIRT1 overexpression inhibited PDCoV replication, whereas mutant SIRT1 lacking deacetylase activity did not affect PDCoV replication. These results indicated that the deacetylation activity of SIRT1 is critical for the anti-PDCoV effects of Res. We also found that Res treatment significantly elevated IFN-β mRNA levels and activated IRF3 phosphorylation via SIRT1. In conclusion, Res can activate SIRT1, upregulating the interferon signaling pathway and promoting IFN-β production, thereby inhibiting PDCoV replication. As such, Res may be a promising therapeutic agent for PDCoV control, facilitating the development of novel anti-PDCoV drugs.

2026-01-01·JOURNAL OF ETHNOPHARMACOLOGY

Bovis calculus sativus improves cognitive function after ischemic stroke by regulating PKA/CREB/Sirt1/eIF2α signaling pathway

Article

作者: Wang, Ling-Feng ; Huang, Zhen ; Guo, Ze-Jun ; Zhang, Lei ; Qiu, Feng-Mei ; Chu, Tan-Lu ; Lv, Shu-Rui ; Zhong, Xiao-Ming ; Zhang, Shu-Yuan ; Guo, Wan-Yu

ETHNOPHARMACOLOGICAL RELEVANCE:

Bovis calculus sativus (BCS) is a traditional medicinal agent known for its pharmacological properties, which include heat-clearing, mental faculty revitalization, liver-cooling, and anticonvulsant effects. It is widely used application in the treatment of ischemic stroke accompanied by cognitive impairment; however, further research is necessary to clarify its effects and underlying mechanisms.

AIM OF THE STUDY:

This study examined the therapeutic potential of BCS in mitigating ischemic stroke-induced cognitive impairment induced by ischemic stroke, focusing on its mechanism of action in enhancing synaptic plasticity via the PKA/CREB/Sirt1/eIF2α signaling pathway.

METHODS:

ICR mice were randomly allocated into six groups: sham-operated, model, edaravone (EDA), and BCS at dosages of 5, 10, and 15 mg/kg. The global cerebral ischemia/reperfusion (GCI/R) model was established using double-vessel occlusion combined with hypotension. Cognitive function was assessed through eight-arm maze and novel object recognition tests. Histological alterations in the hippocampal CA1 region were assessed via hematoxylin-eosin (HE) staining, while neuronal morphology was analyzed using Golgi staining. The expression levels of Synapsin1 (SYN1), postsynaptic density-95 (PSD95), phosphorylated protein kinase A (p-PKA), phosphorylated cAMP response element-binding protein (p-CREB), silent mating type information regulation 2 homolog-1 (Sirt1), phosphorylated eukaryotic initiation factor 2α (p-eIF2α), and phosphorylated protein kinase-like endoplasmic reticulum kinase (p-PERK) were quantified through Western blot analysis. In vitro, PC12 cells subjected to oxygen-glucose deprivation/reperfusion (OGD/R) were treated with BCS and the Sirt1 inhibitor EX527 was employed to elucidate the mechanism of action.

RESULTS:

BCS (10 and 15 mg/kg) significantly improved cognitive performance, reduced memory errors (P < 0.05), and increased dendritic branching and spine density (P < 0.001). Histological analysis revealed a significant loss of neurons in the model group, while BCS treatment significantly preserved neuronal integrity (P < 0.001). BCS increased p-PKA levels, thereby activating CREB transcriptional activity and upregulating Sirt1 expression. Moreover, BCS suppressed the PERK/eIF2α pathway, elevating PSD95 and SYN1 expression. This promoted synaptic remodeling and restored cognitive function after ischaemic injury. In the OGD/R model, BCS restored PSD95, SYN1, and Sirt1 expression (P < 0.001), whereas EX527 markedly reduced their expression (P < 0.01). In contrast, p-eIF2α expression was significantly higher in the model group (P < 0.001) but decreased after BCS treatment. EX527 raised the p-eIF2α levels again (P < 0.05).

CONCLUSION:

BCS appears to enhance hippocampal synaptic plasticity, possibly via the PKA/CREB/Sirt1/eIF2α pathway, which may promote neuronal survival and partially improve cognitive function in ischemic stroke models. These findings suggest that BCS could be a potential therapeutic agent for stroke-induced cognitive impairment.

2026-01-01·JOURNAL OF ETHNOPHARMACOLOGY

Cornuside ameliorates LPS induced cognitive dysfunction and microglial NLRP3 inflammasome activation by enhancing Sirt1-mediated autophagy

Article

作者: He, Jun ; Tong, Zhuohang ; Yuan, Xiaotang ; Zhou, Fulin ; Zhang, Weiku ; Xu, Jiekun ; Lian, Wenwen ; Cheng, Yungchi

ETHNOPHARMACOLOGICAL RELEVANCE:

Corni fructus are the fruits of Cornus officinalis Sieb. et Zucc. and is widely used in traditional Chinese Medicine for the treatment of dementia. Cornuside, derived from Corni fructus, has been shown to be effective in improving cognition of AD mouse.

AIM:

In the present study, we investigated the effect of cornuside on cognitive dysfunction and microglial NLRP3 inflammasome activation, as well as explored the underlying mechanism with respect to Sirt1 and autophagy.

METHODS:

AD mice were established and then treated with cornuside (3, 10, and 30 mg/kg) for 2 weeks. A series of behavioral tests were performed to assess cognition, including the Morris water maze, Y maze, nest building, step-down and step-through tests. Nissl staining was used to evaluate neuronal structural damage. LPS-stimulated BV2 cells were used for in vitro experiments. The anti-inflammatory effects of cornuside on cytokines and NLRP3 inflammasome activation were assessed using ELISA, RT-PCR, immunohistochemistry, western blotting, and immunofluorescence assays. To further elucidate the relationship between Sirt1, autophagy, and NLRP3 inflammasome activation, EX527 and 3-MA were used to inhibit Sirt1 and block autophagy flux in vitro, respectively.

RESULTS:

Cornuside significantly improved various behavioral performance and inhibited NLRP3 inflammasome activation in LPS-induced mice, as evidenced by decreased levels of NLRP3, ASC, pro-caspase1, caspase1, pro-IL-1β, IL-1β, GSDMD, GSDMD-NT and IL-18. Similar inhibitory effects of cornuside on NLRP3 inflammasome activation was also detected in LPS stimulated BV2 cells. The involvement of Sirt1 and autophagy were further explored in-vivo and in-vitro, revealing that cornuside increased the expression of Sirt1 and enhanced autophagy, with decreased SQSTM1/p62 and increased LC3BII. However, the inhibitory effect of cornuside on NLRP3 inflammasome activation was abrogated by 3-MA, and the effects of cornuside on promoting autophagy and inhibiting NLRP3 inflammasome activation was abolished by EX527.

CONCLUSION:

Cornuside exerts therapeutic effects on LPS induced AD mice by inhibiting microglial activation and NLRP3 inflammasome overactivation. And Sirt1 mediated autophagy activation is a vital mechanism by which cornuside degrades NLRP3 inflammasome, thereby alleviating neuroinflammation and improving cognitive function.

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