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Endocrinology and Metabolic Disease

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Endocrinology and Metabolic Disease	1

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Small molecule drug	1

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GSK-3β(Glycogen synthase kinase-3 beta)	1

Binge eating is defined as eating abnormally large amounts in a brief period of time. Many animal studies have examined the behavioural and physiological effects of binge eating of high-fat, high-sugar foods to model the consequences of human binge eating. The present systematic review of 199 rodent studies sought to identify the behavioural and physiological consequences of binge eating and determine whether changes were specific to binge eating or to general effects of exposure to a palatable diet. A meta-analysis of 18 rodent studies revealed that binge eating produces greater anxiety-like behaviour on the Elevated Plus-Maze with a small effect size and significant funnel plot asymmetry, suggesting that the true effect size is overestimated. A history of binge-like access generally increases progressive ratio breakpoint for the binged food, without altering 'liking' as measured by lick microstructure, suggesting that dissociable effects on 'wanting' but not 'liking' accompany binge eating behaviour and contribute to its persistence. Binge eating appears to enhance compulsive food-seeking behaviour and prevent stress-induced reductions in intake but does not appear to alter depression-like behaviour or locomotor activity. Notably, binge eating may produce comparable metabolic impairments to those observed after extended continuous exposure to a palatable diet despite no overall effects on body weight outcomes in most studies.

01 Apr 2025·Animal Models and Experimental Medicine

Establishment and characterization of liver‐specific Apoa4‐Cre and Cyp2c11‐Cre rat models in juvenile and adult stages

Article

Author: Zhang, Li ; Guan, Feifei ; Zhang, Lianfeng ; Chen, Wei ; Dong, Wei ; Pan, Jirong ; Gao, Xiang

AbstractBackgroundLiver diseases are a major contributor to both morbidity and mortality. Conditional knockout animals are always produced through crossing floxed animals with a tissue‐specific Cre animal. The use of floxed rat resource has rapidly increased, but the liver‐specific Cre rat lines for studying liver diseases and interested genes are limited, especially in a spatially and temporally restricted manner.MethodsRNA sequencing and real‐time polymerase chain reaction (PCR) were used to screen and confirm the presence of liver‐specific genes. Apoa4‐Cre rats and Cyp2c11‐Cre rats were produced by CRISPR/Cas9 knockin. Rosa26‐imCherry rats were employed to hybridize with the Cre rats to obtain the Apoa4‐Cre/Rosa26‐imCherry and Cyp2c11‐Cre/Rosa26‐imCherry rats. The temporal and spatial patterns of Cre expression were determined by the observation of red fluorescence on tissue sections. Hematoxylin–eosin stain was used to evaluate the liver histopathologic changes. The blood biochemical analysis of several liver enzymes and liver lipid profile was performed to evaluate the liver function of Cre rats.ResultsApoa4 and Cyp2c11 were identified as two liver‐specific genes. Apoa4‐Cre and Cyp2c11‐Cre rats were produced and hybridized with Rosa26‐imCherry rats. The red fluorescence indicated that the Cre recombinases were specially expressed in the juvenile and adult liver and not in other organs of two hybridized rats. All the blood biochemical parameters except low‐density lipoprotein (LDL) did not change significantly in the Cre rats. No histological alterations were detected in the livers of the Cre rats.ConclusionsLiver‐specific Apoa4‐Cre and Cyp2c11‐Cre rats have been established successfully and could be used to study gene knockout, specifically in juvenile and adult liver.

01 Apr 2025·Drug Development Research

A Novel Oxo‐Palmatine Derivative 2q as Potent Reversal Agents Against Alzheimer's Disease

Article

Author: Zhang, Guo‐jun ; Pang, Shuo ; Luo, Zhuo‐Hui ; Yang, Ya‐Jun ; Chen, Jun ; Fan, Songqiao ; Li, Zhuo ; Liu, Ning ; Shi, Junjie ; Pan, Shuo ; Liu, Ao ; Yin, Heqing

ABSTRACTPalmatine (PAL), as an active ingredient in traditional Chinese medicine, had been demonstrated efficacy in ameliorating the manifestations of AD. Our research group has previously designed and synthesized the novel oxo‐PAL derivative 2q and found that it has exhibited notable neuroprotective properties. However, compound 2q therapeutic impact on AD remains uncertain. In the current investigation, our findings demonstrated that compound 2q displayed significant anti‐AβOs activity in vitro by using xCELLigence analysis, and showed a high likelihood of crossing the blood‐brain barrier. Furthermore, administration of compound 2q yielded a notable amelioration in Aβ accumulation and hyperphosphorylation of Tau in 3×Tg mice. Additionally, it was observed that compound 2q potentially enhanced the pathological characteristics of AD by targeting Potassium/Sodium Hyperpolarization‐Activated Cyclic Nucleotide‐Gated Channel 2 (HCN2). In conclusion, compound 2q emerged as a promising candidate for AD treatment, as it effectively restored AD‐associated pathological impairments. Furthermore, it has been identified as a potential target of HCN2, thereby offering novel avenues for the development of treatments for AD.

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100 Translational Medicine associated with Institute of Laboratory Animal Science

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Pipeline

Pipeline Snapshot as of 19 Dec 2025

The statistics for drugs in the Pipeline is the current organization and its subsidiaries are counted as organizations,Early Phase 1 is incorporated into Phase 1, Phase 1/2 is incorporated into phase 2, and phase 2/3 is incorporated into phase 3

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