The present study was designed to investigate the role and mechanism of the Apoptosis repressor with caspase recruitment domain (ARC) in protecting the neomycin-induced hair cell damage. HEI-OC1 cells and basilar membrane culture were applied to determine the effect of ARC. Plasmid transfection was used to regulate the ARC or Ras expression. We have found the ARC overexpression in HEI-OC1 cells can increase the cell viability and decrease cell apoptosis after neomycin injury. The cleaved caspase 3 was reduced in ARC overexpression group after neomycin treatment. The p-CREB expression was increased in ARC overexpression group, while the p-c-Jun expression was decreased after neomycin incubation. In HEI-OC1 cells and basilar membranes, JNK and Ras inhibitions both can reduce ARC expression, and Ras overexpression can increase the ARC expression. This study indicates that ARC can protect the hair cells from neomycin-induced apoptosis through Ras/JNK signaling pathway. Our findings provide new insights in preventing cochlear HC death after drug-induced ototoxicity.

01 Dec 2024·Ultrasonics

Pathology reduction and motor behavior improvement associated with ultrasound-mediated delivery of arctiin to the motor cortex in a mutant SOD1 mouse model of amyotrophic lateral sclerosis

Article

Author: Chen, Siping ; Zou, Liangyu ; Chen, Kaili ; Yang, Xifei ; Hua, Lingchen ; Chen, Yizhe ; Li, Shupeng ; Zhang, Ji ; Shen, Yuanyuan ; Chen, Xin

BACKGROUNDAmyotrophic lateral sclerosis (ALS) is marked by the deterioration of both cortical and spinal cord motor neurons. Despite the underlying causes of the disease remain elusive, there has been a growing attention on the well-being of cortical motor neurons in recent times. Focused ultrasound combined with microbubbles (FUS/MB) for opening the blood-brain barrier (BBB) provides a means for drug delivery to specific brain regions, holding significant promise for the treatment of neurological disorders.OBJECTIVESWe aim to explore the outcomes of FUS/MB-mediated delivery of arctiin (Arc), a natural compound with anti-inflammatory activities, to the cerebral motor cortex area by using a transgenic ALS mouse model.METHODSThe ALS mouse model with the SOD1^G93A mutation was used and subjected to daily Arc administration with FUS/MB treatment twice a week. After six-week treatments, the motor performance was assessed by grip strength, wire hanging, and climbing-pole tests. Mouse brains, spinal cords and gastrocnemius muscle were harvested for histological staining.RESULTSCompared with the mice given Arc administration only, the combined treatments of FUS/MB with Arc induced further mitigation of the motor function decline, accompanied by improved health of the gastrocnemius muscle. Furthermore, notable neuroprotective effect was evidenced by the amelioration of motor neuron failure in the cortex and lumbar spinal cord.CONCLUSIONThese preliminary results indicated that the combined treatment of FUS/MB and arctiin exerted a potentially beneficial effect on neuromuscular function in the ALS disease.

01 Sep 2024·BMJ Open Ophthalmology

Alterations in anterior lens capsule structure and LTBP-2 expression in primary angle-closure glaucoma

Article

Author: Yuan, Liyun ; Tian, Xiaofeng ; Yuan, Xiaoyong ; Li, Liangpin

ObjectiveThis study investigated the role of latent-transforming growth factor β-binding protein 2 (LTBP-2) in primary angle-closure glaucoma (PACG) by analysing its expression and the ultrastructure of the anterior lens capsule in PACG patients with age-related cataract (ARC).MethodsTissue samples of the anterior lens capsule were collected from patients undergoing cataract phacoemulsification surgery. Patients in the experimental group were diagnosed with primary angle-closure (PAC) combined with ARC (PAC+ARC) and PACG combined with ARC (PACG+ARC). The control group consisted of patients with only ARC. The techniques used included scanning electron microscopy, real-time fluorescence quantitative polymerase chain reaction (RT-qPCR), western blotting and immunofluorescence.ResultsUltrastructural analysis revealed disordered connections in PAC+ARC, loose connections in PACG+ARC and well-ordered connections in ARC. RT-qPCR and western blotting showed significantly lower LTBP-2 mRNA and protein expression in PAC+ARC and PACG+ARC than in ARC, with PAC+ARC having the lowest levels. Immunofluorescence confirmed these findings, showing varying LTBP-2 fluorescence intensities across groups.ConclusionThe study identified ultrastructural changes in the anterior lens capsules in PACG accompanied by reduced LTBP-2 expression, especially in PAC+ARC patients. This suggests a potential role for LTBP-2 in PACG development, warranting further investigation.

100 Deals associated with Prasterone/Estradiol/Drospirenone

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Indication	Highest Phase	Country/Location	Organization	Date
Sexual Dysfunctions, Psychological	Phase 3	-	Pantarhei Bioscience BV	-
Sexual Dysfunctions, Psychological	Phase 3	-	ANI Pharmaceuticals, Inc.	-
Pregnancy	Discovery	NL	Pantarhei Bioscience BV	03 Feb 2019
Female sexual dysfunction	Discovery	NL	Pantarhei Bioscience BV	24 Jan 2019

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1114 (ESH2012)	Not Applicable	ARC \| aldosterone \| MR	-	ARC (Aldosterone)	mnnoaddgwh(tyzogbxomm) = wjxmibsinm mdlaiwkxha (hoosqqltzi )	-	01 Sep 2012
				Spironolactone 10 nM	mnnoaddgwh(tyzogbxomm) = bxwyuovdui mdlaiwkxha (hoosqqltzi )

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