[Translation] Multiple intravenous administration of anabolic steroid injection in subjects with severe pneumonia: a randomized, double-blind, placebo-controlled phase I clinical study

评价SCAP受试者多次静脉给予不同剂量的安脑三醇注射液的安全性、耐受性及药代动力学（PK）特征，并初步探索其有效性

[Translation]

To evaluate the safety, tolerability and pharmacokinetic (PK) characteristics of multiple intravenous administration of different doses of anabolic steroid injection to SCAP subjects, and to preliminarily explore its effectiveness

Start Date01 Apr 2023

Sponsor / Collaborator

Guangzhou Cellprotek Pharmaceutical Co., Ltd.

ChiCTR2400088887 / CompletedPhase 2IIT

A Phase IIa trial of Androtriol Injection for the Treatment of Acute Ischemic Stroke -a Prospective, Multicenter, Randomized, and Placebo-controlled Study

Start Date10 Nov 2021

Sponsor / Collaborator-

CTR20192127 / Active, not recruitingPhase 2

安脑三醇注射液治疗急性缺血性卒中Ⅱa期临床试验——前瞻性、多中心、随机、双盲、安慰剂平行对照研究

[Translation] Phase IIa clinical trial of anabolic steroid injection in the treatment of acute ischemic stroke: a prospective, multicenter, randomized, double-blind, placebo-controlled study

初步探索安脑三醇注射液治疗急性缺血性卒中（AIS）的有效性，并观察其对AIS患者的安全性。

[Translation]

To preliminarily explore the effectiveness of anencephalotriol injection in the treatment of acute ischemic stroke (AIS) and observe its safety in AIS patients.

Start Date10 Nov 2021

Sponsor / Collaborator

Guangzhou Cellprotek Pharmaceutical Co., Ltd.

100 Clinical Results associated with VDCCs x mGluRs

100 Translational Medicine associated with VDCCs x mGluRs

0 Patents (Medical) associated with VDCCs x mGluRs

141

Literatures (Medical) associated with VDCCs x mGluRs

01 Sep 2024·Ophthalmology Retina

Congenital Stationary Night Blindness

Article

Author: Mahroo, Omar A ; Georgiou, Michalis ; Katta, Mohamed ; Fujinami, Kaoru ; Webster, Andrew R ; de Guimaraes, Thales A C ; Fujinami-Yokokawa, Yu ; Michaelides, Michel

OBJECTIVETo examine the molecular causes of Schubert-Bornschein (S-B) congenital stationary night blindness (CSNB), clinically characterize in detail, and assess genotype-phenotype correlations for retinal function and structure.DESIGNRetrospective, longitudinal, single-center case series.PARTICIPANTSOne hundred twenty-two patients with S-B CSNB attending Moorfields Eye Hospital, United Kingdom.METHODSAll case notes, results of molecular genetic testing, and OCT were reviewed.MAIN OUTCOME MEASURESMolecular genetics, presenting complaints, rates of nystagmus, nyctalopia, photophobia, strabismus, color vision defects and spherical equivalent refraction (SER). Retinal thickness, outer nuclear layer (ONL) thickness, and ganglion cell layer + inner plexiform layer (GCL+IPL) thickness from OCT imaging.RESULTSX-linked (CACNA1F and NYX) and autosomal recessive (TRPM1, GRM6, GPR179 and CABP4) genotypes were identified. The mean (± standard deviation) reported age of onset was 4.94 ± 8.99 years. Over the follow-up period, 95.9% of patients reported reduced visual acuity (VA), half had nystagmus, and 64.7% reported nyctalopia. Incomplete CSNB (iCSNB) patients more frequently had nystagmus and photophobia. Nyctalopia was similar for iCSNB and complete CSNB (cCSNB). Color vision data were limited but more defects were found in iCSNB. None of these clinical differences met statistical significance. There was no significant difference between groups in VA, with a mean of 0.46 logarithm of the minimum angle of resolution, and VA remained stable over the course of follow-up. Complete congenital stationary night blindness patients, specifically those with NYX and TRPM1 variants, were more myopic. CACNA1F patients showed the largest refractive variability, and the CABP4 patient was hyperopic. No significant differences were found in OCT structural analysis during the follow-up period.CONCLUSIONSRetinal structure in CSNB is stationary and no specific genotype-structure correlates were identified. Visual acuity seems to be relatively stable, with rare instances of progression.FINANCIAL DISCLOSURE(S)Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.

01 Aug 2024·Journal of Ethnopharmacology

Study on analgesic effect of Shentong Zhuyu Decoction in neuropathic pain rats by network pharmacology and RNA-Seq

Article

Author: Xia, Dongbin ; Chen, Peng ; Gong, Qian ; Wu, Lulu ; Chen, Lukui ; Wang, Chen ; Wang, Xilong ; Lin, Jian ; Xie, Huiling

ETHNOPHARMACOLOGICAL RELEVANCEShentong Zhuyu Decoction (STZYD) is a traditional prescription for promoting the flow of Qi and Blood which is often used in the treatment of low back and leg pain clinicall with unclear mechanism. Neuropathic pain (NP) is caused by disease or injury affecting the somatosensory system. LncRNAs may play a key role in NP by regulating the expression of pain-related genes through binding mRNAs or miRNAs sponge mechanisms.AIM OF THE STUDYTo investigate the effect and potential mechanism of STZYD on neuropathic pain.METHODSChronic constriction injury (CCI) rats, a commonly used animal model, were used in this study. The target of STZYD in NP was analyzed by network pharmacology, and the analgesic effect of STZYD in different doses (H-STZYD, M-STZYD, L-STZYD) on CCI rats was evaluated by Mechanical withdrawal thresholds (MWT) and thermal withdrawal latency (TWL). Meanwhile, RNA-seq assay was used to detect the changed mRNAs and lncRNAs in CCI rats after STZYD intervention. GO analysis, KEGG pathway analysis, and IPA analysis were used to find key target genes and pathways, verified by qPCR and Western Blot. The regulatory effect of lncRNAs on target genes was predicted by co-expression analysis and ceRNA network construction.RESULTSWe found that STZYD can improve hyperalgesia in CCI rats, and H-STZYD has the best analgesic effect. The results of network pharmacological analysis showed that STZYD could play an analgesic role in CCI rats through the MAPK/ERK/c-FOS pathway. By mRNA-seq and lncRNA-seq, we found that STZYD could regulate the expression of Cnr1, Cacng5, Gucy1a3, Kitlg, Npy2r, and Grm8, and inhibited the phosphorylation level of ERK in the spinal cord of CCI rats. A total of 27 lncRNAs were associated with the target genes and 30 lncRNAs, 83 miRNAs and 5 mRNAs participated in the ceRNA network.CONCLUSIONSTZYD has the effect of improving hyperalgesia in CCI rats through the MAPK/ERK/c-FOS pathway, which is related to the regulation of lncRNAs to Cnr1 and other key targets.

01 May 2024·Veterinary Ophthalmology

Additional evidence supports GRM6 p.Thr178Met as a cause of congenital stationary night blindness in three horse breeds

Article

Author: Finno, Carrie J. ; Esdaile, Elizabeth ; Thomasy, Sara ; Motta, Monica J. ; Gilger, Brian C. ; Sandmeyer, Lynne ; Ferneding, Michelle ; Story, Brett D. ; Bellone, Rebecca R. ; Donnelly, Callum G. ; Avila, Felipe ; Knickelbein, Kelly E.

AbstractCongenital stationary night blindness (CSNB) is an ocular disorder characterized by nyctalopia. An autosomal recessive missense mutation in glutamate metabotropic receptor 6 (GRM6 c.533C>T, p.(Thr178Met)), called CSNB2, was previously identified in one Tennessee Walking Horse and predicted to reduce binding affinity of the neurotransmitter glutamate, impacting the retinal rod ON‐bipolar cell signaling pathway. Thus, the first aim was to identify the allele frequency (AF) of CSNB2 in breeds with reported cases of CSNB and breeds closely related to the Tennessee Walking Horse. The second aim was to perform ocular examinations in multiple breeds to confirm the link between genotype and CSNB phenotype. In evaluating 3518 horses from 14 breeds, the CSNB2 allele was identified in nine previously unreported breeds. The estimated AF was highest in pacing Standardbreds (0.17) and lowest in American Quarter Horses (0.0010). Complete ophthalmic examinations and electroretinograms (ERG) were performed on 19 horses from three breeds, including one CSNB2 homozygote from each breed. All three CSNB2/CSNB2 horses had an electronegative ERG waveform under scotopic light conditions consistent with CSNB. The remaining 16 horses (seven CSNB2/N and nine N/N) had normal scotopic ERG results. All horses had normal photopic ERGs. This study provides additional evidence that GRM6 c.533C>T homozygosity is likely causal to CSNB in Tennessee Walking Horses, Standardbreds, and Missouri Fox Trotting Horses. Genetic testing is recommended for breeds with the CSNB2 allele to limit the production of affected horses. This study represents the largest across‐breed identification of CSNB in the horse and suggests that this disorder is likely underdiagnosed.

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