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Shh pathway regulation and control biological rhythm and related application thereof

A biological rhythm and pathway technology, applied in the field of treatment and research of rhythm-related diseases, can solve problems such as Shh signaling pathway regulating biological rhythm

Pending Publication Date: 2022-06-28
ACADEMY OF MILITARY MEDICAL SCI
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0005]However, there are no reports on the Shh signaling pathway regulating biological rhythms and treating rhythm-related diseases

Method used

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  • Shh pathway regulation and control biological rhythm and related application thereof
  • Shh pathway regulation and control biological rhythm and related application thereof
  • Shh pathway regulation and control biological rhythm and related application thereof

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0138] Example 1. The performance of SCN region-specific knockout Smo mice in the change of light cycle

[0139] 8-week-old adult female mice were housed individually in a cabinet equipped with a running wheel cage, and ClockLab was used to record and analyze the running wheel behavior of the mice in real time. figure 1 A is a representative result of the corresponding mouse wheel running behavior. After the mice were acclimated to a standard light cycle (lights on at 7:00 in the morning and lights off at 19:00 in the evening) for two weeks, the light schedule was advanced 8 hours (lights on at 23:00 in the evening). , turn off the lights at 11:00 am), after 15 days of observation, return the light schedule to the initial state. In the figure, the mouse running wheel behavior is represented by black marks, and the white and gray backgrounds represent light and darkness, respectively; figure 1 B is the statistical result of the phase shift of the corresponding mice during t...

Embodiment 2

[0141] Example 2. Identification of SCN region-specific knockout Smo mice

[0142] NMS-Cre is a tool mouse that specifically expresses Cre in the SCN region, and Smo is an important receptor in the Shh signaling pathway. By mating NMS-Cre mice with Smo-floxp mice, NMS-Smo– / – small mice were obtained after multiple generations of breeding. mouse.

[0143] figure 2 A is the Western Blot to detect the effect of Smo knockout (Smo is not only expressed in NMS neurons in the SCN area, so the results show that after the specific knockout of Smo in the SCN area, there is still a small amount of detection); figure 2 B shows that the body weight of Smo conditional knockout mice is not affected; figure 2 C shows that the overall outline of the brain of the Smo conditional knockout mouse is normal; figure 2 D and 2E show normal neuronal differentiation in the SCN region of Smo conditional knockout mice.

[0144]The above results prove that the Smo mouse with a specific knockout ...

Embodiment 3

[0145] Example 3. The Smo inhibitor Vismodegib affects the rhythmic behavior of mice

[0146] Vismodegib is a novel oral drug with selective Shh signaling pathway. The results show that Vismodegib can directly affect the oscillatory changes of rhythm genes, block the SCN neuron coupling process, and make mice adapt more quickly. Time difference change process. image 3 A: The rhythm gene affects the oscillating changes of the rhythm gene in the SCN region at the tissue level. Freshly isolated brain slices in the SCN region of Per2::Luc mice were used for in vitro culture, and the expression level of Per2 was continuously recorded by lumicycle; after three days of recording, the medium was changed to In the fresh medium containing 20 μM Vismodegib, it was observed that Vismodegib could significantly inhibit the oscillating change process of Per2; three days later, the drug was removed and replaced with fresh medium, and it was found that the oscillating Per2 was restored, ind...

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Abstract

The invention relates to the technical field of biology, in particular to Shh pathway regulation and control biological rhythm and related application thereof. Specifically, the invention provides application of a Hedgehog pathway inhibitor and an SMO inhibitor in regulating the biological rhythm and treating diseases related to the biological rhythm. Preferably, the Hedgehog pathway inhibitor comprises the following components: PF-5274857, Mebendazole, HPI-4, SANT-1, Taladegib, Grasdegib, Cyclopamine, Itracazole, GANT61, JK184, Robotnikinin, Vismodegib, Purmorphamine, and Sonidegib Phoshate, and the Hedgehog pathway inhibitor comprises the following components: PF-5274857, the Mebendazole, the HPI-4, the SANT-1, the Taladegib, the Grasdegib, the Cyclopamine, the Itracazole, the GANT61, the JK184, the Robotnikinin, the Vismodegib, the

Description

technical field [0001] The invention relates to the field of biotechnology, in particular to the Shh pathway regulating biological rhythm, and can be used for the treatment of rhythm-related diseases. Background technique [0002] Biological sleep, wakefulness, eating and other behaviors, as well as various physiological, biochemical, and metabolic processes follow about 24-hour rhythmic changes, commonly known as the biological clock, which is closely related to the normal physiological functions of the human body. Studies have shown that biological rhythms are closely related to many physiological indicators such as individual sleep, diet, cognition, emotion, behavior, metabolism, etc., which are related to the coordination and orderly performance of the entire body and adaptation to the environment. If the normal biological rhythm is disrupted , will lead to the abnormality of the body's psychological and physiological functions, and at the same time will cause the dysfun...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): A61K45/06A61K31/4402A61K31/506A61K31/437A61K31/5377A61K31/496A61K31/4184A61K31/517A61K31/502A61K31/454A61K31/58A61K31/395A61P25/20A61P25/24A61P3/00A61P7/00A61P3/10A61P3/04A61P39/06A61P25/00A01K67/027A01K67/02
CPCA61K45/06A61K31/4402A61K31/506A61K31/437A61K31/5377A61K31/496A61K31/4184A61K31/517A61K31/502A61K31/454A61K31/58A61K31/395A61P25/20A61P25/24A61P3/00A61P7/00A61P3/10A61P3/04A61P39/06A61P25/00A01K67/0275A01K67/02A01K2227/105A01K2267/03A01K2267/0356A61K2300/00
Inventor 李慧艳涂海情周涛李爱玲吴敏胡怀斌何新华张学敏
Owner ACADEMY OF MILITARY MEDICAL SCI
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