The present work was conducted to evaluate the pharmacological effect of Arctiin(ARC) on high fat diet(HFD)-induced Non-alcoholic steatohepatitis(NASH) and investigate its potential mechanism. The network pharmacology and bioinformatic analyses predicted that FGFR2 might be the potential target of ARC. Palmitic acid(PA)-induced AML12 cell was employed as the in vitro model. ARC reduced the levels of ALT, AST, TC, TG, and attenuated histopathological alteration. ARC inhibited inflammatory cytokines, inflammatory molecules, downregulated the expressions of FGFR2/CSF1R, inhibited glycolysis and promoted oxidative phosphorylation both in vivo and in vitro. ARC enhanced mitochondrial membrane potential and reduced oxidative stress. The application of FGFR2-OE plasmid, CSF1R-OE plasmid, CSF1R inhibitor PLX indicated that ARC attenuated glycolysis and inflammation in PA-induced AML12 cells via FGFR2/CSF1R signaling. HIF1A was proved to be involved in this process using HIF1A agonist DEF and HIF1A inhibitor PX478. Molecular docking and molecular dynamic suggested that ARC might combine with FGFR2. In conclusion, the present study demonstrated that ARC ameliorated NASH by inhibiting glycolysis and inflammation via FGFR2/CSF1R signaling.

01 Mar 2025·Pediatric Infectious Disease Journal

Therapeutic Drug Monitoring of High-dose Sulbactam in Pediatric Patients: Preliminary Data From a Prospective Observational Pharmacokinetic Study

Article

Author: Chatsuwan, Tanittha ; Anugulruengkitt, Suvaporn ; Wacharachaisurapol, Noppadol ; Puthanakit, Thanyawee ; Charoenwong, Kankamol ; Suchartlikitwong, Pintip ; Sukkummee, Warumphon ; Sophonphan, Jiratchaya

Background:Rates of carbapenem-resistant Acinetobacter baumannii are rising in Thailand. Although high-dose (HD) sulbactam is recommended for treating carbapenem-resistant A. baumannii infections, data on plasma sulbactam concentrations in children are limited. We aimed to evaluate plasma sulbactam concentrations and pharmacokinetic-pharmacodynamic (PK-PD) target achievement in pediatric patients.Methods:Prospective study data (January–November 2023) on children (1 month–18 years) who received sulbactam every 6–8 hours were analyzed. Mid-dosing (Cmid, 50% fT) and trough (Ctrough, 100% fT) concentrations were evaluated. PK-PD target achievement [50% fT > minimum inhibitory concentration (MIC), 100% fT > MIC] was evaluated using Clinical and Laboratory Standards Institute 2024 MIC cutoffs and MIC data of isolates of Acinetobacter calcoaceticus–baumannii complex from this study.Results:Thirty-five patients (median age 50 months) were categorized into standard-dose (SD) or HD groups. The geometric mean Cmid was higher in the HD (41.3 mg/L) versus SD (19.5 mg/L) groups (P = 0.006). Among 101 isolates of Acinetobacter calcoaceticus–baumannii complex, the MIC50 and MIC90 (concentrations that inhibit 50% and 90% of isolates of the A. calcoaceticus–baumannii complex) were 16 and 128 mg/L, respectively. The HD group achieved Cmid >MIC50 in 87.5% of the patients compared with 63.6% in SD (P = 0.17). Within the HD group, patients with augmented renal clearance (ARC) had lower Cmid (geometric mean 31.9 mg/L) compared with non-ARC (geometric mean 63.4 mg/L) (P = 0.04).Conclusions:HD sulbactam resulted in higher Cmid and PK-PD achievement. ARC significantly compromised plasma sulbactam concentration. HD sulbactam may be preferable for treating critically ill pediatric patients and those with ARC, especially during the empirical period.

01 Jan 2025·Toxicology Letters

ARC protects cochlear hair cells from neomycin-induced ototoxicity via the Ras/JNK signaling pathway

Article

Author: Lou, Xiangyu ; Zhang, Jie ; Fang, Qiaojun ; Kang, Wenjie ; Guan, Ming ; Yu, Xiaoyu ; Shang, Haiqiong ; Gao, Hanbing

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.

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	Netherlands	Pantarhei Bioscience BV	03 Feb 2019
Female sexual dysfunction	Discovery	Netherlands	Pantarhei Bioscience BV	24 Jan 2019

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Study	Phase	Population	Analyzed Enrollment	Group	Results	Evaluation	Publication Date


1114 (ESH2012)	Not Applicable	ARC \| aldosterone \| MR	-	ARC (Aldosterone)	hlfkmqkogn(wubyzukpxc) = npiwnpyhxa vvmhgoiros (lzpytmhgtd )	-	01 Sep 2012
				Spironolactone 10 nM	hlfkmqkogn(wubyzukpxc) = ecxnopxkwl vvmhgoiros (lzpytmhgtd )

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